Homer proteins control neuronal differentiation through IP(3) receptor signaling.
Neurons expand, sustain or prune their dendritic trees during ontogenesis [Cline, H.T. (2001). Dendritic arbor development and synaptogenesis. Curr. Opin. Neurobiol. 11, 118-126; Wong, W.T. and Wong, R.O.L. (2000) Rapid dendritic movements during synapse formation and rearrangement. Curr. Opin. Neurobiol. 10, 118-124] which critically depends on neuronal activity [Wong, W.T., Faulkner-Jones, B.E., Sanes, J.R. and Wong, R.O.L. (2000) Rapid dendritic remodeling in the developing retina: dependence on neurotransmission and reciprocal regulation by Rac and Rho. J. Neurosci. 20, 5024-5036; Li, Z., Van Aelst, L. and Cline, H.T. (2000) Rho GTPases regulate distinct aspects of dendritic arbor growth in Xenopus central neurons in vivo. Nat. Neurosci. 3, 217-225; Wong, W.T. and Wong, R.O.L. (2001) Changing specificity of neurotransmitter regulation of rapid dendritic remodeling during synaptogenesis. Nat. Neurosci. 4, 351-352.] and sub-cellular Ca(2+) signals [Lohmann, C., Myhr, K.L. and Wong, R.O. (2002) Transmitter-evoked local calcium release stabilizes developing dendrites, Nature 418, 177-181.]. The role of synaptic clustering proteins connecting both processes is unclear. Here, we show that expression levels of Vesl-1/Homer 1 isoforms critically control properties of Ca(2+) release from intracellular stores and dendritic morphology of CNS neurons. Vesl-1L/Homer 1c, an isoform with a functional WH1 and coiled-coil domain, but not isoforms missing these features were capable of potentiating intracellular calcium signaling activity indicating that such regulatory interactions function as a general paradigm in cellular differentiation and are subject to changes in expression levels of Vesl/Homer isoforms.
Tanaka
Masahiko
M
Division of Cell Biology, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan.
Duncan
R Scott
RS
McClung
Nathalie
N
Yannazzo
Jo-Ann S
JA
Hwang
Sung-Yong
SY
Marunouchi
Tohru
T
Inokuchi
Kaoru
K
Koulen
Peter
P
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002352:Carrier Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D003712:Dendrites; D000072233:Homer Scaffolding Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D020033:Protein Isoforms / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013569:Synapses; D014162:Transfection
D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; C000606624:Homer1 protein, rat; D053496:Inositol 1,4,5-Trisphosphate Receptors; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D002118:Calcium