Abstract
The dendritic tree is a key determinant of neuronal information processing. In the motor system, the dendritic tree of spinal cord neurons undergoes dramatic remodeling in an activity-dependent manner during early postnatal life. This leads to the proper segmental spinal cord connectivity that subserves normal locomotor behavior. One molecular system driving the establishment of dendrite architecture of mammalian motor neurons relies on AMPA receptors (AMPA-Rs) assembled with the GluA1 subunit, and this occurs in an NMDA receptor (NMDA-R)- independent manner. The dendrite growth promoting activity of GluA1-containing AMPA-Rs depends on its intracellular binding partner, SAP97, and SAP97’s PDZ3 domain. We show here that cysteine-rich interactor of PDZ3 (CRIPT) is a bona fide SAP97 PDZ3-domain binding partner, localizes to synapses with GluA1 and SAP97 along the dendritic tree, and is a determinant of the dendritic growth of mammalian spinal cord neurons. We further show that CRIPT has a well-conserved ortholog in the nematode, Caenorhabditis elegans, and animals lacking CRIPT display decreased dendrite branching of the well-studied PVD neuron in vivo. The lack of CRIPT leads to a selective defect in touch perception, and this is rescued by expression of wild-type (WT) human CRIPT (hCRIPT) in the nervous system. This work brings new light into the molecular machinery that drives dendritic growth during development and may prove relevant to the promotion of nervous system plasticity following insult.
Original language | English (US) |
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Article number | e0175-17.2017 |
Journal | eNeuro |
Volume | 4 |
Issue number | 6 |
DOIs | |
State | Published - Nov 1 2017 |
Funding
Received May 19, 2017; accepted October 30, 2017; First published November 27, 2017. The authors declare no competing financial interests. Author contributions: L.Z., A.M.J., J.M.-P., I.P.N., Y.S., and R.G.K. designed research; L.Z., A.M.J., J.M.-P., H.D., I.P.N., J.Z., Y.S., and R.G.K. performed research; R.L.N. contributed unpublished reagents/analytic tools; L.Z., A.M.J., S.S., I.S.N., M.Z., and R.G.K. analyzed data; L.Z. and A.M.J. wrote the paper. This work was supported by Public Health Service Grants NS087077and NS052325 (to R.G.K.) and F31-NS07726 (to A.M.J.), the Cancer Research UK Program Grant C430/A11243 (to I.N. and I.P.N.), and the RGC of Hong Kong Grant AoE-M09-12 (to M.Z.). *L.Z. and A.M.J. contributed equally to this work. J. Zhai’s present address: Gene Therapy Program, University of Pennsylvania, 125 S 31st Street, Suite 1300, Philadelphia, PA 19104-3403. R. G. Kalb’s present address: Davee Department of Neurology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611-4296. Acknowledgements: We thank Maria Lim, John Flibotte, and Marco Boccitto for technical assistance and for useful discussion; Yina Dong and David Lynch for the gift of antibodies and plasmids to NR1, NR2A, NR2B, NR2C, and NR2D; Maria Passafaro for the gift of the CRIPT plasmids; and David Miller for the gift of the PPVD::GFP worms. Some of the Caenorhabditis elegans strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40-OD010440). Some strains were also provided by Shohei Mitani (National BioResource Project (NBRP)::C. elegans.). Correspondence should be addressed to Robert Gordon Kalb at the above address, E-mail: [email protected] or [email protected]. DOI:http://dx.doi.org/10.1523/ENEURO.0175-17.2017 Copyright © 2017 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. This work was supported by Public Health Service Grants NS087077 and NS052325 (to R.G.K.) and F31-NS07726 (to A.M.J.), the Cancer Research UK Program Grant C430/A11243 (to I.N. and I.P.N.), and the RGC of Hong Kong Grant AoE-M09-12 (to M.Z.).
Keywords
- AMPA
- CRIPT
- Dendrite
- Development
- GluA1
- Motor
ASJC Scopus subject areas
- General Medicine