Biology Reference
In-Depth Information
In the central domain, at the base of the growth cone, a dense microtu-
bule array extends from the neurite shaft. In addition to structural support,
microtubules support the bidirectional, transport of biosynthetic and
endocytic vesicular cargos essential to growth cone function and remodeling
(
Rajagopal et al., 2007
). Additionally, microtubules direct local exo- and
endocytotic vesicle cycling in the growth cone, (
Sann, Wang, Brown, &
Jin, 2009
) primarily regulated in the central domain (
Diefenbach, Guthrie,
Stier, Billups, & Kater, 1999
). Dynamic microtubules extend from the
central domain through the transition zone, which separates the central
and peripheral domains, and deliver vesicular cargos necessary to support
the F-actin-driven protrusive activity characteristic of the peripheral do-
main. In the actin-rich, peripheral domain, the cytoskeletal assembly of actin
mesh-works drives thin sheet-like, lamellipodial, veil-like, protrusions, and
the assembly of actin bundles drives, spike- or finger-like, filopodial protru-
sions (
Jornvall et al., 2004; Kamiguchi, 2006
) critical to advancing the
growth cone but
also critical
to regulating
the
spatiotemporal
organization of the growth cone's receptors and CAMs.
How do protrusions regulate receptor and cell adhesion distribution?
During active growth cone remodeling, lamellipodia and filopodia are
key to the cyclical exocytotic delivery and endocytic return of membrane
vesicles harboring receptor and CAM complexes between the central
domain of the growth cone and the extracellular environment (e.g.,
Fig. 2.2
).
During lamellar and filopodial protrusion, F-actin assembly drives the
plasma membrane outward as exocytotic vesicles fuse with the expanding
plasma membrane adding their lipids and protein cargos to the protrusions
(
Itofusa & Kamiguchi, 2011
). As protrusions advance, receptors and CAMs
are delivered peripherally to the extracellular environment. Subsequently,
lamellipodia and filopodia that retract carry both activated and inactivated
receptors and unbound CAMs back to the central domain. There they
are endocytosed into various vesicles and then sorted for recycling and a
return trip to the plasma membrane, degradation, local signaling in the
growth cone, or long-distance retrograde signaling in the neurite and soma.
Sorting decisions are likely based on endosomes' individual signaling
profiles, as discussed below for neurotrophin signaling endosomes.
How do protrusions direct vesicle trafficking to influence the direction
of neurite growth? Protrusions that deliver CAMs that anchor to molecules
in the extracellular matrix can stabilize lamellar and filopodial protrusions
and thus provide new cytoplasmic conduits that can engorge with vesicular
cargos. These cargos may be directed by locally stabilized microtubules, and
