Homer proteins control neuronal differentiation through IP(3) receptor signaling

FEBS Lett. 2006 Nov 13;580(26):6145-50. doi: 10.1016/j.febslet.2006.10.013. Epub 2006 Oct 17.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Signaling
  • Carrier Proteins / analysis
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Cell Differentiation*
  • Dendrites
  • Homer Scaffolding Proteins
  • Inositol 1,4,5-Trisphosphate Receptors / metabolism*
  • Nerve Tissue Proteins / physiology
  • Neurons / cytology*
  • Neurons / metabolism
  • Protein Isoforms / analysis
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Rats
  • Rats, Wistar
  • Signal Transduction*
  • Synapses
  • Transfection


  • Carrier Proteins
  • Homer Scaffolding Proteins
  • Homer1 protein, rat
  • Inositol 1,4,5-Trisphosphate Receptors
  • Nerve Tissue Proteins
  • Protein Isoforms
  • Calcium