F

FAK see focal adhesion kinase fatty-acid linked proteins 48 FC

- caveolae 102-104

- changes 104-106

- interactions 94 FC binding

- proteins 101-102

- structural aspects 101

FC depletion, effects on caveolar proteins 102

FC recognition sites, signal transduction 99 FC-rich vacuoles, increased endocytosis 103 FCCS see fluorescence cross-correlation spectroscopy FCS see fluorescence correlation spectroscopy fibroblasts

- phase separation 10

- signaling pathways 125 fibronectin, phosphorylation 128 filamin 127

- identification 199

filipin, cholesterol localization 182 filopodia, focal adhesion complex 198-199

fission-fusion processes, endocytosis 73 FL-DOPE 52 fl-PE 52

FLIP, endocytosis 72 flotillins, signal transduction 96 flow cytometric FRET, lipid rafts 162 fluid membranes, physical modeling 26-29 fluid-mosaic model 45-46 fluorescein phosphatidylethanolamine see fl-PE

fluorescence correlation spectroscopy (FCS) 57-59, 147

- diffusion-based measurements 52

- mobility measurements 161 fluorescence cross-correlation spectroscopy

(FCCS) 147

- mobility measurements 161 fluorescence distributions, overlap 144-145 fluorescence lifetime, FRET 147 fluorescence loss in photobleaching see FLIP fluorescence microscopy 144-145 fluorescence recovery after photobleaching

- endocytosis 72

fluorescence resonance energy transfer 59, 145

focal adhesion complex, caveolin 198-199 focal adhesion kinase (FAK) 199, 256-257 Foerster's resonance energy transfer see

FRET formation

- endothelial tube 241

- PrPSc 210-211

- stress fiber 195-202

- supramolecular protein complexes 141-174

- vesicle 15 Förster distance 146

Förster's resonance energy transfer see FRET FRAP see fluorescence recovery after photo-bleaching free-cholesterol-binding sites, peptide contributions 100 free endocytic vesicles, caveolar function 83 free energy (F), physical modeling of lipid membranes 26 FRET 4, 6-7, 16, 145

- efficiency 145

- flow cytometric 162

- immunological synapse 151

- lipid rafts 157

- pb see pbFRET

- proximity measurements 60 frustration, bilayer order 31-32 Frye-Edidin experiment 155 functional multiprotein complexes 103 functional suppression, caveolin-1 in cancer cells 252-254 functional unit 142 Fyn

- activation 132

- caveolin phosphorylation 121

- expression 119

- inhibition 125-127

- overexpression 122

Fyn-Abl, interaction 122-123 g gangliosides 93

gate theory of aging 195

gel state, lipids in membranes 49-50

genetic suppression, caveolin-1 in cancer cells 252-254 GFP 6

- proximity measurements 60 GFP-tagged caveolin 71

giant unilamellar vesicle (GUV)

- fluorescence correlation spectroscopy 57

- membrane model system 3

- raft domains 9

glucose transport, stimulation 131 glucose transporter 4 (GLUT4)

- caveolin 199-200

- translocation 131

glutathione S-transferase (GST)-CSD fusion proteins 235 glycoproteins, immunological synapse 151

glycosphingolipid GM1 ganglioside, lipid microdomains 164 glycosphingolipids 9

- raft hypothesis 45 glycosyl-phosphatidyl-inositol see GPI GM1 gangliosides, distribution 160 GPI, membrane traffic 4, 6-8 GPI-anchor

- proximity measurements 60

- PrPc 207-208

- raft hypothesis 48

- transmembrane signaling 143 GPI-anchored proteins 8, 48, 51, 54, 63, 92,

- caveolae 175

- raft immobilization 84

- signal transduction 92

green fluorescent protein see GFP growth conditions, caveolae structure 96 growth factor, vascular endothelial 241 growth factor-mediated signaling 104 GST see glutathione S-transferase GTP-binding proteins, TC10 200 GUV see giant unilamellar vesicle h

H-Ras, FRAP 56 HA, single-molecule tracking 54 hairy-aspect, caveolae 25 HASM 53

HDL see high-density lipoprotein

HDL uptake, caveolin-1 182

heart, role of nitric oxide 234

heart rate regulation, muscarinic cholinergic

244-245 HeLa cells, endocytosis 79 hemagglutinin see HA hetero-FRET 6

- proximity measurements 62-63 heteroclusters, cell fusion 156 heterodimerization, lipid rafts 157 heterologous expression, caveolin-1 in cancer cells 252-254 hexamethylglutaryl coenzyme A (HMGCoA) 240

high-density lipoprotein (HDL) 239

- estrogen 185

- signal transduction 94 HMGCoA reductase inhibitors (statins)

240-241 homeoproteins, endocytosis 183 homo-FRET 6

- proximity measurements 60-62 homo-oligomers, caveolins 33 homoclusters

- cell fusion 156

- immunological synapse 152 Hooke's law, physical modeling of lipid membranes 27 hop diffusion, single-molecule tracking 54

human cancer, role of caveolin-1 251 human coronary artery smooth muscle see HCASM

human epidermal carcinoma see KB human myoepithelial cells 70 human T lymphoma cells, lipid rafts 157 hydrophobic regions, membrane proteins 31

hyperphosphorylation, caveolin phosphoryla-tion 118

ICAM-1, co-localization 153

IGF-I see insulin-like growth factor-I

- co-localization 159, 162

- raft assisted signaling 159 IL-2, lipid rafts 156-162 IL-6 254-255

immunolocalization, caveolae 179, 182 immunological synapse (IS) 150 inclusions

- due to sorting signals 15

- membrane 31-34

incompatibility (chemical), influence on lipid domain shape 29-30 independent pathways, endocytosis 84 inducible NOS isoform (iNOS) 234 inhibition, Fyn 125-127 iNOS see inducible NOS isoform insulin absence 70

insulin in adipocytes, signaling pathways 116-117

insulin-induced actin remodeling 131 insulin-induced caveolin phosphorylation 119

insulin-like growth factor-I (IGF-I) 254-255 insulin receptor, caveolins 117-118 integrins, focal adhesion complex 198-199 interleukin see IL intermixing, cell fusion 155 internalization 75

- caveolae 81-82

- PrPc 209-210

intracellular caveolin-associated structures, caveosomes 82-83 intracellular chaperone complexes 175-194 intracellular compartments

- amyloid b-peptide (Ab) 215-217

- PrPc conversion 208-210 intracellular polarity 195-196 invaginated caveolae, equilibrium 92 invaginated lipid rafts, caveolae 28-31 invaginated membrane domains, bending energy 30 invaginations, caveolar 84-85 IS see immunological synapse k

K-Ras, FRAP 56

K+ channels, voltage-gated 154-155 KB, signal transduction 94 kinases 127

- caveolin 120, 129

- caveolin tyrosine 123

- focal adhesion 199, 256-257

- non-receptor tyrosine 119

- phosphoinositide 254-256

- receptor 106

- receptor tyrosine 163-166

- Src-family see Src-family kinase

- tyrosine 116, 119

kiss-and-run, transendothelial transport 74 l labeled molecules, local concentration 148 lactase-phlorizin hydrolase see LPH lag time, FCS 148 large unilamellar vesicles see LUV latranaculin A, FRAP 56 LAURDAN, amphiphilic dye 5 LDL see low-density lipoprotein line tension 13

linear pathway, caveolin phosphorylation 121 lipid-anchored proteins 48 lipid bilayer 1, 141

- structure 28

lipid components, cellular membranes 2,

143-144, 175 lipid composition, caveolae 12 lipid domain shape, influence of chemical incompatibility 29-30 lipid membrane 141

- artificial 50

- bilayer structure 28

- physical modeling 26-29

- see membranes lipid microdomains 141-174

- receptor tyrosine kinases 163-166 lipid phosphate phosphohydrolase, signal transduction 94 lipid rafts 1-17, 51-52, 141, 143, 156-162, 175

- biophysical characterization 45-68

- co-localization 153

- invaginated 28-31

- membrane traffic 12-17

- planar 92

- processing of prion protein 205-223

- signal transduction 91

- voltage-gated K+ channels 154-155 lipid uptake, caveolin 188

lipids, two-dimensional fluids 45 lipoproteins, caveolin-eNOS interaction 239-241

liquid crystalline state, lipids in membranes 49-50

liquid-disordered phases 3-5

liquid-ordered phases 3-5

- lipid rafts 92 loading, FC 102-104

local motility, endocytosis 73-74 local regulatory processes 154-155 localization

- caveolae 182-183

- caveolin 178-182, 187

- cholesterol 182-183

- co- see co-localization locomotion, roles of caveolae and caveolin 195-202

low-density lipoprotein (LDL) 103

- cholesterol 239-241

LPH, single-molecule tracking 54 lung cancer, role of caveolin-1 251 LUV 3

lysotracker, caveosomes 82 m mAchR see muscarinic cholinergic macrodomains, lipid 143 macrophage apoptosis, mouse 258 Madin-Darby canine kidney (MDCK)

- endocytosis 72

mammary tumor cells, caveolin-1 expression

252 mbCD 58

MCF-7 cells, caveolin-1 expression 253-254 MDCK see Madin-Darby canine kidney MDR human cancer cells 258 mean barrier-free path, domain size 144 mechano-regulation/-sensitivity, caveolae 38-42

melting temperature, lipid mixtures 3 membrane-associated proteins 49 membrane cap, spherical 28 membrane components 142-143 membrane crossing, caveolin 183-184 membrane domain shape, influence of chemical incompatibility 29-30 membrane domains 45

- bending energy 30

- caveolae 71

- nonendocytic 71

- scaffolded see scaffolded membrane domains membrane extension, actin remodeling 127 membrane inclusions 31-34 membrane interactions, caveolin 177-178 membrane model, Singer-Nicolson 141 membrane molecules, single-molecule tracking 53

membrane phases, fluorescence correlation spectroscopy 57 membrane protein clusters, cell fusion 156 membrane proteins

- aggregation 32

- asymmetric 33-35

- hydrophobic regions 31

- lateral organization 144-149

- reorganization 142

- thermodynamic phase separation 35-38 membrane raft hypothesis, development 48 membrane systems, phase separation 3-5 membrane temperature, effective 27 membrane tension

- caveolae 38-42

- in relation to domain energy and shape 39

membrane topology 48 membrane traffic 1-17

- cargo sorting and vesicle formation 15

- caveolae and lipid rafts 12-17

- cellular organelles 12

membrane transporter proteins 97 membranes

- cell see cell membrane

- detergent-insoluble 50

- detergent-resistant see detergent-resistant membranes (DRM)

- diffusion process 58

- lipid see lipid membrane

- plasma see plasma membrane

- see apical membrane metalloproteases 214 methyl-b-cyclodextrin see mbCD MHC I

- co-localization 153, 162

- homoassociation 151

- transendothelial transport 75 MHC I glycoprotein, domain size 145 microdomains

- cholesterol/sphingolipid (FC/SPH)-rich 91

- lipid 141-174

- plasma membrane 175 microscopy

- atomic force 149

- confocal laser scanning 144

- electron 51

- fluorescence 144-145

- quantitative immunogold labeling electron 71

migratory synapses, immunological synapse 150

mitosis, signal transduction 96 MLV 3

model membrane systems, phase separation 3-5

modeling, lipid membranes 26-29 modulation of polarity, caveolin 195-196 molecular specificity, SNOM 149 molecules

- adhesion 151

- dipole moment 5

- labeled 148

- motion 52

- signaling 133

- single, tracking 53-54 motility, caveolae 73-74

multi-protein complexes, signal transduction 95

multifunctional adaptor proteins 249 multilamellar vesicles see MLV multiphoton excitation, domain size 144 multiprotein complexes, functional 103 multistage caveolin lipidation cycle 105 muscarinic cholinergic (mAchR), heart rate regulation 244-245 mutant caveolin 180, 252

- caveolae formation 37-38 mYFP-GPI, proximity measurements 60 myocytes, cardiac 234, 244-245 myoepithelial cells, human 70

N-terminal

- caveolins 25, 177

- endocytosis 70

N-WASP, actin polymerization 130 NCAM 53

negative data evaluation, caveolae determination 179

neural cell adhesion molecule see NCAM nitric oxide synthase (NOS), endothelial 233-246

NMR see nuclear magnetic resonance NO-mediated vascular relaxation 242-243 non-receptor tyrosine kinases 119 noncaveolar rafts, endocytosis 69 nonendocytic membrane domains, caveolae

nongenomic actions, caveola 185-186 NOS see nitric oxide synthase NOSIP see eNOS interacting protein NOSTRIN see eNOS traffic inducer NPC-1 fibroblasts, cholesterol transport 188

nuclear magnetic resonance (NMR)

- lipid microdomains 163

- lipid rafts 50

o organelles, membrane traffic 12

ovarian cancer cells, pro-apoptotic activity of caveolin-1 253 overexpression techniques, caveolin-1 253 oxidative stress, signaling pathways 125

P132L, mutant caveolin-1 252

partitioned fluid, single-molecule tracking 53

pathways

- APP cleaving 218

- caveolin trafficking 188

- compensatory activation, caveolae 176

- endocytic 84, 176

- PI3K/Akt 254-256

- signaling 116-123 paxillin, signaling pathways 124 pbFRET 146

pbFRET microscopy, lipid microdomains

- DRM 50 PDGF 117

- signal transduction 96 PDGFR, signal transduction 105 PDK1 see phosphoinositide-dependent protein kinase-1 PE 2-3

peptide contributions, free-cholesterol-

binding sites 100 percolating raft membrane 9-10 peripheral SMAC see pSMAC PHA 160

phalloidin, phosphorylation 129 phase diagram (ternary), SM/PC/cholesterol 4

phase separation

- cargo sorting and vesicle formation 15

- caveolin oligomers 38

- cell membranes 5-7

- fibroblasts 10

- model membrane systems 3-5 phases

- liquid-disordered 3-5

- liquid-ordered 3-5

phosphatidic acid, signal transduction 94 phosphatidylcholine see PC phosphatidylethanolamine see PE phosphatidylinositol-3'-phosphate see PI(3)P phosphatidylserine see PS

phosphocaveolin 126-129

- Csk 124-125 phosphocholine see PC phosphoinositide 3-kinase (PI3K), cell survival 254-256 phosphoinositide-dependent protein kinase-1

(PDK1) 255 phospholipase D2, signal transduction 94 phosphoprotein, signaling pathways 124 phosphorylation 115

- actin/plasma membrane attachment sites 128

- caveolin see caveolin phosphorylation

- cell migration 130

- eNOS activity 238

- signaling pathways 116-123

- stable 129

- tyr14 256-257

- tyrosine 116-123 photobleaching

- fluorescence recovery see fluorescence recovery after photobleaching

- FRET 146

phytohemagglutinin see PHA PI(3)P 2

PI3K see phosphoinositide 3-kinase

PI3K/Akt pathway, cell survival 254-256

picket-fence model 54, 56

placental alkaline phosphatase see PLAP

planar lipid rafts, equilibrium 92

plasma membrane 127-129

- fluid-mosaic model 46

- microdomains 175

- protein complexes 141

- see also membranes plasmalemmal vesicles see caveolae plasmalogens, caveolae 94 platelet-derived growth factor see PDGF polarity, modulation by caveolin 195-196 polyacrylamide gel electrophoresis see PAGE polyethylene glycol, artificial frustration 32 potassium channels see K+ channels preadipocytes, caveolin phosphorylation 117 preassembly, IL-chains 157 prebeta-HDL, signal transduction 94 preferred bulb radius, caveolae 36-37 primary cells, differentiated 91

prion conversion, raft action 211-214 prion diseases 205-223 prion proteins

- internalization 81

- processing 205-223

- see also PrPc pro-apoptotic activity, caveolin-1 253 prostate cancer cells, survival-promoting activity of caveolin-1 253-254 proteases, metallo- 214 protein acylation, caveolae 186 protein anchor, raft hypothesis 48 protein clusters, cell fusion 155-156 protein co-mobility 147 protein coats, recyclable 13 protein complexes, supramolecular 141-174 protein organization, caveolae 187 protein patterns, plasma membrane 142 protein-protein interactions, tyrosine phosphorylation 123 protein structure, caveolin 177-178 protein transport, raft hypothesis 49 proteins

- basolateral 14

- caveolae 95-98

- contact site 99

- FC binding 101-102

- GPI-anchored 51

- lipid-anchored 48

- membrane-associated 49

- prion see prion proteins proteolytic attack on PrPc, role of rafts 214 proximity measurements 59-63

PrPc

- lipid rafts 205, 207-214

- see also prion protein

PrPc conversion, role of rafts 208-210 PrPc-PrPSc transconformation 208, 210-214 PrPSc 207

- formation 210-211 PS 2-3

pSMAC, immunological synapse 150 PTEN, tumor suppressor protein 255

q quantitative immunogold labeling electron microscopy, endocytosis 71

r radiolabeled tracers, caveola 184 raft action, prion conversion 211-214 raft-aspect, caveolae 25 raft concept, phase separation in cell membranes 5-7 raft domains, clustered 8-9 raft hypothesis, origin 45-48 raft immobilization, caveolin 84-85 raft integrity 159 raft membrane, percolating 9-10 raft models, current 47

raft signaling., protein acylation 186 rafts

- lipid see lipid rafts

- noncaveolar 69, 75

- role in PrPc conversion 208-210 rapamycin, chaperone complexes 184 rat basophilic leukemia see RBL receptor, insulin binding 117 receptor autophosphorylation, signal transduction 104 receptor families, lipid microdomains 163 receptor kinase, signal transduction 106 receptor tyrosine kinases, function

163-166 recyclable protein coats 13 regulation, caveolin-1 182 regulatory cycle, caveolin-eNOS 236-238 regulatory processes, local 154-155 reorganization, membrane proteins 142 reserve rafts, diffusion-based measurements 55

resolution, SNOM 149 resonance energy transfer process, fluorescence 59 Rho GTPase activity, modulation by caveolin

195, 197-198 rigidity, bending 27-28

Saffman-Delbruck model, single-molecule tracking 54 saturated acyl chains, transmembrane signaling 143 scaffold hypothesis, caveolin 98-101 scaffold motifs, signal transduction 99 scaffold sequence, endothelin receptor-A 99 scaffolded membrane domains

- caveolae 10-12

- caveolin see caveolin scaffolded domain scanning near-field optical microscopy 149 scavenger receptor BI see SRBI scavenger receptors, caveolae 187

SCLC see small-cell lung cancer scrapie PrP see PrPSc SDS-PAGE

- caveolae 177

- lipid rafts 51 SDS-resistant complexes 117 secondary structure, caveolin 177 secretase 215-223

a-secretase, role of caveolae and lipid rafts 220-221

ß-secretase, role of caveolae and lipid rafts 206, 214-218

g-secretase, role of caveolae and lipid rafts 221-222

secretory synapse, immunological synapse 150

Semliki Forest virus, raft hypothesis 49 Ser1177 phosphorylation, eNOS activity 238 sex hormone action, caveola 185 SFK see Src-family kinase SH2 120

SH2-mediated binding, phosphocaveolin 126 shaping forces, caveolae 25-42 Shiga toxin, endocytosis 77 sialidase, signal transduction 95 signal transduction

- caveolae 91-114

- FC changes 104-106 signaling

- caveolae 115-140

- time course 105

- transmembrane 141-174 signaling cascades

- activation 124

- caveolin 115

signaling complexes, caveolin 132 signaling molecules, caveolin phosphoryla-

tion 133 signaling pathways 116-133

- caveolin phosphorylation 121

- phosphorylation 256-257 signaling platforms, lipid rafts 156-162 signaling proteins

- classes 96

- scaffold motif 99 Simian virus 40 (SV40) 200

- raft and caveolar endocytosis 14

- transendothelial transport 74 Singer-Nicolson fluid mosaic membrane model, validity 141 single kinase knockout mice 119 single-molecule studies, diffusion-based measurements 52-55 single-particle tracking 52

- immunological synapse 151

- membrane molecules 53 SM 2-4, 9

small-cell lung cancer (SCLC), role of caveolin-1 251 SNARE, fluorescence correlation spectroscopy 58 SNOM 149, 165 sodium dodecyl sulfate see SDS sodium dodecyl sulfate-polyacryamide gel electrophoresis see SDS-PAGE

sorting signals, cargo sorting and vesicle formation 15 spectroscopic ruler 145 spectroscopy, fluorescence see fluorescence correlation spectroscopy spherical membrane cap 28 sphingolipid-rich microdomains 91 sphingolipids

- APP processing 222

- raft hypothesis 45 sphingomyelin see SM sphingomyelinase, signal transduction 95 spontaneous curvature 27

SPT see single-particle tracking SR-BI, scavenger receptors 187 SRBI 185

Src-family kinase (SFK) 118-119, 127,

256-257

- inhibitors 119

- phosphorylation 130

- regulation 125

- signal transduction 106 Src-homology 2 see SH2

SSR, diffusion-based measurements 55 statins

- reduction of caveolin abundance 240-242

- stimulation of endothelial tube formation 241

statistical confidence, FRAP 56 steady-state anisotropy, proximity measurements 61 sterol uptake, caveolin 188 stress fiber formation, roles of caveolae and caveolin 195-202 stress-induced changes, caveolin-1 expression

257-258

stress-induced pathways, opposing 130 strong cholesterol depletion 216 subcellular locations, caveolin-1 prescence 181

superstructures, ErbB2-containing 164 suppression, caveolin-1 in cancer cells

252-254

supramolecular organization, immunological synapse 150 supramolecular protein complexes

- formation 141-174

- lipid rafts 162

surface scanning resistance see SSR surface tension, lipid membrane 27 survival-promoting activity, caveolin-1

253-254

SV40 see Simian virus 40 syntaxin 3, apical t-SNARE 16

synthases, endothelial nitric oxide 233-246 synthetic lipid bilayers, signal transduction 92

T-cell homeostasis, lipid rafts 156 T-cell receptor see TCR T cells

- activation 154

- raft clustering 8 T lymphocytes 154

T lymphoma cells, human 157

t-SNARE, syntaxin 3 16

TAMRA-4D5-labeled ErbB2 receptors 165

TC10, GTP-binding protein 200

TCR complex, immunological synapse 150

TCZ 52

temperature

- melting, lipid mixtures 3

- membrane 27

ternary phase diagram, SM/PC/cholesterol 4 TfR 156, 160-162 TGFß 82

TGN see trans-Golgi network thermodynamic phase separation, membrane proteins 35-38 Thr495 phosphorylation, eNOS activity 238 Thy-1, GPI-anchored protein 8 TNFa 124

traffic, membrane see membrane traffic trafficking

- caveolin 183-184

- prion protein 205-223 trafficking cycle, caveola 184-185 trafficking pathways, caveolin 188 TRAMP mouse model 253, 256 trans-Golgi network (TGN) 50, 215

- APP cleaving pathways 218

- endocytosis 72

transconformation, PrPc-PrPSc 210-214 transendothelial transport, endocytosis 73-74 transferrin receptor see TfR transforming growth factor beta see TGFß transient confinement zone see TCZ transmembrane proteins 48 transmembrane receptor tyrosine kinases, lipid microdomains 163 transmembrane receptors, signal transduc-tion 96

transmembrane signaling 141-174

- complex 105

transport, transendothelial 73-74 trastuzumab, cancer therapy 165 Trojan peptide 102

tube formation, endothelial 241 tumor cell survival, role of caveolin-1 249-259

tumor necrosis factor-alpha see TNFa tumors, angiogenesis 241-242 tyr14 phosphorylation 256-257 tyrosine, caveolin phosphorylation

116-123 tyrosine kinases 119

- signaling pathways 116

u unidentified intracellular compartment (UIC) 218

v vascular endothelial growth factor (VEGF) 241-242

- signal transduction 97 vascular functions, heart 234 vascular permeability, transendothelial transport 74

vascular relaxation, endothelium-dependent and NO-mediated 242-243 vasodilation, caveolin-eNOS interaction 242-244

VEGF see vascular endothelial growth factor venular endothelial cells, caveolin determination 180

vesicle formation, membrane traffic 15 vesicle trafficking, caveolin 183 vesicular vacuolar organelle see VVO virus, caveolae wave 74 voltage-gated K+ channels, lipid rafts

154-155 VVO, caveolin 180

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Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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