Biology Reference
In-Depth Information
mutation likely introduces a structural defect in the SH3 domain as the same
mutation also blocks cortactin binding to CortBP1 (Shank) (Du et al., 1998).
Interestingly, it appears that both cortactin and Dyn2 are recruited to
peripheral membrane ru
es and lamellipodia in response to the motogenic
growth factor PDGF. Mechanistically, it was demonstrated that the PRD of
Dyn2 is required for targeting to the peripheral rues and that therefore Dyn2
recruitment to the rues is, at least in part, cortactin-dependent. In further
support of this, cortactin lacking the SH3 domain is recruited to membrane
rues and lamellipodia. In contrast to the expression of full-length cortactin,
cells expressing the truncated form do not induce enhanced recruitment of
Dyn2. It is important to note that Dyn2 has been shown to bind to additional
actin regulatory proteins including profilin, Abp1, syndapin, Grb2 and Nck
(reviewed in Orth and McNiven, 2003) and thus these proteins may also play a
role in Dyn2 targeting to and functioning with the actin cytoskeleton. How
Dyn2, together with its actin-associated proteins, regulates membrane ru
ing,
lamellipodium extension and other actin-membrane processes is currently
under intense study.
Participation of dynamin in actin-based membrane dynamics
Dynamin, cortactin and receptor-mediated endocytosis
Perhaps the best characterized function for dynamin is during the endocytosis
of clathrin-coated pits (CCPs) from the plasma membrane. The actin
cytoskeleton is believed to contribute to the formation of clathrin-coated
pits by recruiting proteins that perform a direct role in the process, or by
aiding in the deformation of the donor membrane and/or movement of the
nascent vesicle away from the membrane (Qualmann et al., 2000; Schafer,
2002). How this cytoskeletal network might interact with the endocytic
machinery to regulate vesicle formation and scission remains unclear. A recent
study reported that clathrin, dynamin and actin are sequentially recruited to
forming CCPs, and that there is a rapid accumulation of actin on the bud or
vesicle as it forms and moves away from the plasma membrane (Merrifield et
al., 2002). This study demonstrated an accumulation of dynamin and actin at
the forming endocytic intermediate but did not directly link the endocytic and
cytoskeletal machineries. As Dyn2 participates in the liberation of CCPs from
the plasma membrane and directly binds the actin modulating protein
cortactin, we hypothesized that cortactin could serve as a bridge between the
actin cytoskeleton and endocytic machinery, similar to what has been shown
for Abp1, another dynamin binding partner (Kessels et al., 2001).
Cortactin has been shown to localize within the cell cortex and membrane
ru
es of cultured cells and is most often found at sites of active actin filament
