Long-range inhibitory signaling regulates robust neuronal polarization
T
Takano1,
Mengya
Wu1,
S
Nakamuta1,
H
Naoki2,
N
Ishizawa1,
T
Namba1,
T
Watanabe3,
C
Xu1,
T
Hamaguchi1,
Y
Yura1,
M
Amano1 and
Kozo
Kaibuchi1*
-
1
Nagoya University Graduate School of Medicine, Department of Cell Pharmacology, Japan
-
2
Kyoto University, Imaging Platform for Spatio-Temporal Information, Graduate School of Medicine, Japan
-
3
University of North Carolina, Department of Pharmacology, United States
Neurons are highly polarized cells, which have two structurally and functionally distinct compartments, i.e.axons and dendrites. Correct establishment of axons and dendrites is critical for neuronal network formation, and elucidating the molecular mechanisms. Neuronal polarization is precisely established by robust general mechanisms, local activation signal and long-range inhibitory signaling. Although axon initiation must be accompanied by long-range inhibitory signaling, which suppresses multiple axon formation and thereby determines dendritic specification, less is known about the long-range inhibitory signaling in neuronal polarity. Here, we provided the demonstration of the molecular mechanism of long-range inhibition responsible for neuronal polarization. Local stimulation of the axon with NT-3 induced the retraction of minor neurites, which was caused by a long-range Ca2+ propagation from the axon to the cell body. The Ca2+ propagation induced the polarized activation of RhoA/Rho-kinase in the cell body by the CaMKK/CaMKI pathway. Local inhibition of Rho-kinase in the minor neurites induced rapid neurite elongation and subsequently resulted in multiple axons formation. Furthermore, we performed phospho-proteomic analysis (the KISS method) to identify novel substrates for CaMKI and found that CaMKI phosphorylated RhoA-specific GEF, GEF-H1, and enhanced its GEF activity. Knockdown or a nonphosphorylation mutant of GEF-H1 induced multiple axon formation in hippocampal neurons, and impaired neuronal polarization in developing neocortex. Taken together, long-range signaling of Ca2+/CaMKI/GEF-H1/RhoA/Rho-kinase is a novel inhibitory pathway responsible for the robust establishment of neuronal polarization.
Keywords:
neurone,
molecular mechanism,
polarization,
long-range inhibition,
Ca2+ propagation
Conference:
14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016.
Presentation Type:
Poster Presentation Session
Topic:
14th Meeting of the Asian-Pacific Society for Neurochemistry
Citation:
Takano
T,
Wu
M,
Nakamuta
S,
Naoki
H,
Ishizawa
N,
Namba
T,
Watanabe
T,
Xu
C,
Hamaguchi
T,
Yura
Y,
Amano
M and
Kaibuchi
K
(2016). Long-range inhibitory signaling regulates robust neuronal polarization.
Conference Abstract:
14th Meeting of the Asian-Pacific Society for Neurochemistry.
doi: 10.3389/conf.fncel.2016.36.00114
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Received:
04 Aug 2016;
Published Online:
11 Aug 2016.
*
Correspondence:
Prof. Kozo Kaibuchi, Nagoya University Graduate School of Medicine, Department of Cell Pharmacology, Nagoya, Japan, kaibuchi@med.nagoya-u.ac.jp