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[S25]: HI‐Induced bax translocation to the mitochondria, ER and nucleus correlates with the activation of subcellular cell death signaling cascades
Author(s) -
Gill M.B.,
PerezPolo J.R.
Publication year - 2006
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2006.09.032
Subject(s) - chromosomal translocation , citation , mitochondrion , programmed cell death , apoptosis , neuroscience , library science , biology , microbiology and biotechnology , computer science , genetics , gene
model, we identified a Ser/Thr kinase SAD-1 as a key player in both establishing axon/dendrite polarity and synaptic structures. In C. elegans the loss of the SAD-1 function leads to the accumulation of synaptic vesicles at dendritic regions of neuritis, furthermore, synaptic vesicles are loosely clustered at chemical synapses. Double knockout mouse for SADA and SADB, the two mouse homologues of SAD-1 die immediately after birth, with the cortical and hippocampal neurons fail to differentiate axons and dendrites, suggesting a conserved role of SAD family kinase in establishing neuron polarity. Using genetic and biochemical approaches, we have now revealed components of two distinct genetic pathways through which SAD-1 kinase functions in neural polarity and synaptogenesis. We found that during early differentiation of neurons, SAD-1 physically interacts with a scaffolding protein Neurabin to restrict the axonal fate in neurites. SAD-1/ Neurabin interaction is specifically required for the proper establishment of the polarity, but completely dispensable for synaptogenesis. After the establishment of axons and dendrites, SAD-1 is restricted and regulated at presynaptic region by two novel presynaptic channels unc-7 and unc-77. SAD-1 in turn controls the incorporation of active zone proteins at chemical synapses. These channels affect synapse morphology but do not affect neural polarity. We are further delineating the activator and downstream effectors of the SAD kinase in these two genetic pathways.