Abstract:
:A critical step in neuronal development is the formation of axon/dendrite polarity, a process involving symmetry breaking in the newborn neuron. Local self-amplifying processes could enhance and stabilize the initial asymmetry in the distribution of axon/dendrite determinants, but the identity of these processes remains elusive. We here report that BDNF, a secreted neurotrophin essential for the survival and differentiation of many neuronal populations, serves as a self-amplifying autocrine factor in promoting axon formation in embryonic hippocampal neurons by triggering two nested positive-feedback mechanisms. First, BDNF elevates cytoplasmic cAMP and protein kinase A activity, which triggers further secretion of BDNF and membrane insertion of its receptor TrkB. Second, BDNF/TrkB signaling activates PI3-kinase that promotes anterograde transport of TrkB in the putative axon, further enhancing local BDNF/TrkB signaling. Together, these self-amplifying BDNF actions ensure stable elevation of local cAMP/protein kinase A activity that is critical for axon differentiation and growth.
journal_name
Proc Natl Acad Sci U S Aauthors
Cheng PL,Song AH,Wong YH,Wang S,Zhang X,Poo MMdoi
10.1073/pnas.1115907108subject
Has Abstractpub_date
2011-11-08 00:00:00pages
18430-5issue
45eissn
0027-8424issn
1091-6490pii
1115907108journal_volume
108pub_type
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