TY - JOUR
T1 - Self-amplifying autocrine actions of BDNF in axon development
AU - Cheng, Pei Lin
AU - Song, Ai Hong
AU - Wong, Yu Hui
AU - Wang, Sheng
AU - Zhang, Xiang
AU - Poo, Mu Ming
PY - 2011/11/8
Y1 - 2011/11/8
N2 - 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 ofmany 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.
AB - 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 ofmany 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.
KW - Axon initiation and growth
KW - Neurotrophin autocrine loops
KW - Trk redistribution
KW - cAMP/protein kinase A elevation
UR - http://www.scopus.com/inward/record.url?scp=81055130093&partnerID=8YFLogxK
U2 - 10.1073/pnas.1115907108
DO - 10.1073/pnas.1115907108
M3 - Article
C2 - 22025720
AN - SCOPUS:81055130093
SN - 0027-8424
VL - 108
SP - 18430
EP - 18435
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 45
ER -