Editors' ChoicePhosphatidylinositols

Pipmodulins and PIP2 Availability

See allHide authors and affiliations

Science's STKE  04 Jul 2000:
Vol. 2000, Issue 39, pp. tw3
DOI: 10.1126/stke.2000.39.tw3

Phosphatidylinositol-4,5-bisphosphate (PIP2) is an acidic phospholipid that acts as a messenger to regulate the actin cytoskeleton. Rearrangements in the actin cytoskeleton are involved in cell motility and extension of cellular processes, such as filopodia, lamellapodia, and neurites. Three structurally unrelated proteins, GAP43, CAP23, and MARCKS, share several characteristics that suggest overlapping roles for these proteins in regulating actin dynamics through interactions with PIP2; thus, the name of pipmodulins has been proposed for this group of proteins. Laux et al. show that pipmodulins colocalize with PIP2 in lipid microdomains with characteristics of lipid rafts and control the size of the PIP2 microdomains. Through overexpression studies, the authors found that pipmodulins regulated the formation of neurites and filopodia in a process that depended on the presence of the basic effector domain that allows these proteins to bind PIP2. Laux et al. propose that pipmodulins regulate the accessibility of PIP2, thereby controlling the location and occurrence of cellular processes formed by interactions of the actin cytoskeleton with PIP2. Laux et al. and Frey et al. investigated the role of pipmodulins in vivo using transgenic mice during nerve regeneration. Dominant negative forms of GAP43 disrupted normal neuromuscular junction nerve regeneration. Frey et al. found that GAP43 could functionally substitute for CAP23 in knock in mice, further confirming that these structurally divergent proteins belong to the same functional family.

Laux, T., Fukami, K., Thelen, M., Golub, T., Frey, D., and Caroni, P. (2000) GAP43, MARCKS, and CAP23 modulate PI(4,5)P2 at plasmalemmal rafts, and regulate cell cortex actin dynamics through a common mechanism. J. Cell Biol. 149: 1455-1471. [Abstract] [Full Text]

Frey, D., Laux, T., Schneider, C., and Caroni, P. (2000) Shared and unique roles of CAP23 and GAP43 in actin regulation, neurite outgrowth, and anatomical plasticity. J. Cell Biol. 149: 1443-1453. [Abstract] [Full Text]