INVESTIGADORES
SCORTICATI Camila
congresos y reuniones científicas
Título:
Tyrosine residue 251 is critical for M6a-induced neuroplasticity
Autor/es:
FORMOSO, K; FRASCH, AC; SCORTICATI, C
Lugar:
Huerta Grande
Reunión:
Congreso; Reunion Anual de la SAN; 2012
Institución organizadora:
SAN
Resumen:
Recent findings associate polymorphisms in
human GPM6A with mental illnesses
such as claustrophobia, schizophrenia and bipolar disorders. Neuronal
glycoprotein M6a, coded by GPM6a, is
involved in neuronal plasticity promoting neurite and filopodia outgrowth and,
likely, synaptogenesis. Nevertheless, the molecular basis underlying
these observations remains unknown. Previously, we documented that M6a depends
on membrane lipid microdomains association and activation of Src and MAPK
kinases for filopodia induction. In
silico analysis of phosphorylation of the tyrosine-251 at C-termini of M6a
showed that it could be a target of Src kinases. Thereby, we examined whether
phosphorylation/dephosphorylation at Y251 of M6a affects neurite and filopodia outgrowth
and the possible targets involved in their signal propagation. We show
that phosphorylation of M6a at Y251 residue positively contributes to neurite
extension in primary hippocampal neurons and N2a cells. During this
process Src and AKT are phosphorylated and recruited to the cell membrane. Expression
of a non-phosphorylatable form of M6a totally arrested neurite outgrowth. At
difference with neurites extension, phosphorylation/dephosphorylation of Y251
has no effect on M6a stimulated filopodia formation in neurons and COS-7 cells.
Although, PI3K inhibitors, LY294002 and wotmannin, dramatically blocked filopodia
induction in M6a-overexpresing neurons. The
Ras family of GTPases is not involved in neurite extension neither filopodia
induction promoted by M6a. We
suggest that phosphorylation of M6a at tyrosine 251 is critical for a specific stage of neuronal development and triggers redundant intracellular signaling pathways such as Src and PI3K/AKT leads neurite extension.