Biology Reference
In-Depth Information
Fazzari, 2011; Myers & Gomez, 2011
). Moreover, in nonneuronal cells, the
cytosolic nonreceptor protein tyrosine phosphatase (PTPD1) localizes to
actin as well as to focal adhesions, where it recruits Src, which modulates
FAK and focal adhesion dynamics. Both PTPD1 and Src are transported
on EGFR signaling endosomes during cell migration (
Carlucci et al.,
2010; Tu et al., 2010
). Both FAK and Src-family kinases have also been
localized to Rab5 early signaling endosomes during cell migration
(
Schiefermeier, Teis, & Huber, 2011
). MAP kinase signaling complexes,
downstream effectors of adhesions (
Pullikuth & Catling, 2007
), are also
associated with late endosomes (
Taub, Teis, Ebner, Hess, & Huber, 2007
).
Further support that signaling endosomes regulate adhesions comes from
studies on APPL1. APPL1 impairs migration by hindering adhesion
turnover at the leading edge of cells by inhibiting Akt activity at the plasma
membrane and within adhesions (
Broussard et al., 2012
). In zebrafish, a
subset of Rab5-containing endosomes lacks EEA1 and instead contains
APPL1 and APPL2 as Rab5-effectors (
Schenck et al., 2008
). Finally,
several CAMs, including activated leukocyte cell adhesion molecule
(ALCAM), are transported in signaling endosomes together with
neurotrophins like NGF. ALCAM potentiates neurotrophin signaling
raising the possibility that ALCAM functions not only as an adhesion
molecule but also in modulating the action of NGF (
Wade et al., 2012
),
suggesting a close bidirectional regulation between neurotrophin and
adhesion signaling. In summary, signaling from signaling endosomes not
only allows for the spatial restriction of plasma membrane initiated
signaling but also enables the assembly of distinct signaling complexes
regulating actin dynamics through effector localization and adhesion
formation/breakdown and signaling. However, a direct link between
many of these molecules including FAK and signaling endosomes is still
currently lacking in growth cones.
4. NANOPARTICLE-MEDIATED SIGNALING ENDOSOME
MANIPULATION
4.1. Methodology and characterization
How does signaling endosome
localization
in the growth cone regulate
motility? The potential roles that neurotrophin signaling endosomes play
in regulating membrane trafficking, cytoskeletal effector localization, adhe-
sion dynamics, and even local translation indicate neurotrophin signaling
endosome localization is critical to regulating growth cone motility. To test
