Caveolin and Polarity

Animal cells adopt a vast diversity of shapes, ranging from the relatively simple-looking columnar epithelial cell to the highly complex branched structure of a neuron. Shape and migration are highly dependent on the external environmental conditions for the directional cues that drive intracellular polarity. All eukaryotic

Fig. 9.1 Cellular motility. Cells move through the polarized and dynamic re-organization of the actin cytoskeleton, involving a protruding force at the front (blue arrows), combined with a contractile force in the cell body (green double-headed arrows). Caveolin-1 (red) accumulates at the leading edge and involves polarization during cell movement. N = nucleus.

cells are able to polarize in response to cues at the plasma membrane, for example during the budding of yeast, asymmetrical cell division, and mammalian cell differentiation [8].

Caveolin-1 may play an important role in cell motility because it exhibits anterior-posterior polarization during cell migration. Caveolin-1 was found to accumulate at the leading edge of cultured fibroblasts [9] and human umbilical vein smooth muscle cells [10]. Caveolae and lipid rafts also exhibit pronounced polarity during cell migration (Fig. 9.1), with raft-associated ganglioside GM1 being found at the leading edge of human adenocarcinoma MCF-7 cells, when stimulated with insulin growth factor-1 (IGF-1) [11]. Endothelial cells (ECs) exhibit a polarized distribution of caveolin-1 when traversing a filter pore [12]. In these cells, caveolin-1 seems to be released from the caveolar structure in the cell rear and to be re-localized at the cell front; this is in contrast to the situation that occurs during planar movement, when caveolin-1 is concentrated at the rear of endothelial cells, co-localized with caveolae. Phosphorylation of the Tyr14 residue of caveolin-1 is also required for polarization of the protein during transmigration [12]. Therefore, the localization and phosphorylation of caveolin might play a crucial role in the polarity of cellular morphological changes, although the molecular mechanism involved is, as yet, unclear.

Leading edge

Caveolin-1

Fig. 9.1 Cellular motility. Cells move through the polarized and dynamic re-organization of the actin cytoskeleton, involving a protruding force at the front (blue arrows), combined with a contractile force in the cell body (green double-headed arrows). Caveolin-1 (red) accumulates at the leading edge and involves polarization during cell movement. N = nucleus.

Protrusion

Leading edge

Caveolin-1

Protrusion

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