Biology Reference
In-Depth Information
recycling endosomes play an important part in regulating integrin trafficking
and function (
Arjonen, Alanko, Veltel, & Ivaska, 2012; Caswell et al., 2009;
Pellinen & Ivaska, 2006
). It is also evident that endocytosis and recycling
are important processes involved in mediating growth cone adhesion and guid-
ance (
Itofusa & Kamiguchi, 2011; Tojima, Hines, Henley, & Kamiguchi,
2011
) during axon growth. Exocytosis is also an important part of growth
cone formation. Axon growth cannot proceed without addition of new
membrane coupled with cytoskeletal reorganization, and addition of new
membrane by exocytosis is usually accompanied by insertion of membrane
proteins (
Bradke et al., 2012
). The retraction bulbs that form after injury
contain disorganized microtubules and accumulations of Golgi-derived traf-
ficking vesicles. The giant axons of
Aplysia californica
regenerate in culture,
and manage to convert a retraction bulb into a growth cone after the Golgi-
derived vesicles trapped in the bulb are inserted into the plasma membrane
(
Erez et al., 2007
). A lack of exocytosis might therefore limit axon regener-
ation. There is evidence that favoring exocytosis increases regeneration; for
instance, overexpression of reggie/flotillin proteins allows for robust axon
regeneration. These are a pair of proteins (Reggie1 and 2 or Flotilin2 and 1,
respectively) that were found to be upregulated in goldfish retinal ganglion
cells after optic nerve lesion and have subsequently been shown to be im-
portant for axon regeneration and neurite growth in fish and mammals
(
Stuermer, 2010, 2012
). Reggies are lipid raft-associated proteins that are
involved in the targeted delivery of membrane and/or membrane proteins
to specific microdomains of the cell surface that have been implicated in
growth cone development through the delivery of N-cadherin to the
growth cone surface (
Bodrikov, Solis, & Stuermer, 2011
). This is mediated
by the GTPase TC10, and an interaction with the exocyst component
Exo70. TC10 and Exo70 form a complex of proteins that are essential for
membrane expansion and axon growth during development (
Dupraz
et al., 2009
). Successful regeneration mediated by reggie proteins therefore
involves exocytosis of adhesion molecules, which contribute to growth cone
formation.
Exocytosis is important for integrin-dependent growth during develop-
ment as axon initiation on laminin requires Vamp-7-mediated exocytosis
(
Gupton & Gertler, 2010
). The precise mechanisms controlling integrin in-
sertion into the growth cone membrane have not been established, although
there is a role for targeting from endosomes marked by Rab11. The Rab11
effector Rab-coupling protein (RCP) is involved in targeting
b
1 integrins
onto the surface of cancer cells (
Caswell et al., 2008
), and a GFP-tagged
