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relationship between signaling endosomes and Rac and Cdc42 localization
in growth cones remains largely unstudied.
3.3. Adhesion formation, signaling, and turnover
In growth cones, adhesion-mediated signaling influences the motile dynam-
ics of the growth cone both locally and globally by anchoring the cytoskel-
eton and by organizing cytoskeletal effectors regulating cytoskeletal
assembly and disassembly (
O'Connor, Duerr, & Bentley, 1990; Steketee
& Tosney, 2002
). Growth cone adhesions are dynamic complexes
(
Dequidt et al., 2007
) whose regulated turnover is critical for growth
cones (
Myers et al., 2011
) and cell movement in general (
Huttenlocher &
Horwitz, 2011
). As growth cones advance, adhesions assemble and
disassemble and change in number, size, and distribution (
Myers et al.,
2011; Thoumine et al., 2008
). During lamellar and filopodial protrusion,
CAMs and receptors, including IgCAM, L1, and integrins, are packaged
in vesicles, exocytosed at the leading edge of growth cones, and carried
forward as protrusions advance to interact with extracellular matrix
molecules (e.g.,
Fig. 2.2
). As the growth cone advances, CAM- and
integrin-mediated adhesions are endocytosed and recycled back to the
growth cone surface through Rab11-positive endosomes (
Eva et al.,
2010
)
Fig. 2.3B
). Thus, the polarized distribution and activities of
adhesions are critical to growth cone steering.
How do signaling endosomes regulate the molecular complexes respon-
sible for adhesion assembly maintenance, and disassembly? Generally, mod-
ifying adhesion dynamics affects overall growth, whereas locally modifying
adhesions affects growth cone steering (
Hines et al., 2010; Myers & Gomez,
2011; Woo & Gomez, 2006
). Evidence suggests that signaling endosomes
may regulate molecular activities controlling adhesion dynamics locally.
For example, during turning, growth cone point contacts are
asymmetrically regulated by FAK in response to BDNF (
Myers & Gomez,
2011
). BDNF accelerates paxillin-containing point contact turnover and
formation, further supporting a hypothesis that neurotrophin signaling
endosomes regulate adhesion dynamics. FAK is upstream of numerous
signaling pathways inside the cell, including Src-family kinases, Rho-
family GTPases, actin regulatory molecules, adhesion components, and
microtubules (
Chacon & Fazzari, 2011; Mitra, Hanson, & Schlaepfer,
2005
). In growth cones, localized regulation of FAK has been implicated
in both attractive and repulsive signaling (
Bechara et al., 2008; Chacon &
