Biology Reference
In-Depth Information
Subsequently, Rab5-positive endosomes are either transported retro-
gradely to the soma or further sorted either into Rab11 recycling endo-
somes, returning receptors back to the cell surface, or to Rab7 late
endosomes which may be also be transported retrogradely to the soma
(
Deinhardt et al., 2006; Gruenberg & Maxfield, 1995; Vonderheit &
Helenius, 2005; Zerial & McBride, 2001
), shuttled to lysosomes or
packaged in multivesicular bodies (MVBs) depending on the route of
endocytosis and cellular context (
Philippidou et al., 2011
). Packaging Trk
endosomes into MVBs is intriguing since such packaging could
conceivably preserve Trk endosome integrity during retrograde transport
(
Philippidou et al., 2011
), which is postulated for Pincher-mediated
macroendocytosis of other pro- and antigrowth molecules like Nogo
(
Joset, Dodd, Halegoua, & Schwab, 2010
). However, other studies
suggest that MVBs may reflect
in vitro
conditions since MVBs are rarely
observed
in vivo
in either the CNS or the PNS in the absence of
nonphysiological “dystrophic” stimuli (
Altick, Baryshnikova, Vu, & von
Bartheld, 2009; Von Bartheld & Altick, 2011
). Moreover, once an MVB
reaches the soma, a mechanism for unpackaging is lacking. Nevertheless,
the association with different Rab-family members appears to be one
critical early event in Trk endosomal sorting.
Do neurotrophin-Trk endosomes have distinct signaling profiles that
dictate their sorting? Though Trk activation at the plasma membrane is suf-
ficient to signal changes in the growth cone, the nascent endosome is im-
mature. The endosomal maturation and sorting mechanisms in the
growth cone are largely unknown. However, the speed and precision with
which endosomes are formed and sorted in growth cones suggest that endo-
somes acquire a specific identity early. During active growth cone remo-
deling, lamellipodia and filopodia can initiate, protrude, and retract back
to the central domain on the scale of seconds to minutes in culture
(
Steketee & Tosney, 1999
). Therefore, growth cones must employ efficient
mechanisms for rapidly sorting endocytic vesicles into the appropriate
endosomal compartment.
Considering the inherent complexity of endocytic vesicles due to unique
lipid and protein combinations, ligand/receptor compliments, and extracel-
lular solute composition (
Schenck et al., 2008; Stenmark, 2009
), how are
endocytic vesicles sorted into distinct endosomal compartments?
Conceptually, vesicles could be differentially sorted into early, recycling,
and late endosomes based on unique molecular or signaling profiles. For
instance, does
the number of active Trk complexes per endosome
