TY - JOUR
T1 - Novel phospho-switch function of delta-catenin in dendrite development
AU - Baumert, Ryan
AU - Ji, Hong
AU - Paulucci-Holthauzen, Adriana
AU - Wolfe, Aaron
AU - Sagum, Cari
AU - Hodgson, Louis
AU - Arikkath, Jyothi
AU - Chen, Xiaojiang
AU - Bedford, Mark T.
AU - Waxham, M. Neal
AU - McCrea, Pierre D.
N1 - Funding Information:
Use of the A1-Nikon (confocal images) was made possible via the UT MDACC Department of Genetics NIH Instrumentation Grant 1S10OD024976-01 (A. Paulucci-Holtzhauzen). Probing of arrayed PDZ domains was made possible via the UT MDACC Protein Array and Analysis Core CPRIT Grant RP180804 (M.T. Bedford). Assistance with DNA sequencing was provided from National Cancer Institute Core Grant CA-16672 to UT MDACC. This work was supported by NIH grants RO1GM107079 (P.D. McCrea), RO1GM129098 (L. Hodgson), and 1RO1MH115717 (P.D. McCrea and M.N. Waxham). P.D. McCrea also acknowledges an Ashbel Smith Professorship Award, and M.N. Waxham an endowment from the William Wheless III Professorship. The authors declare no competing financial interests.
Publisher Copyright:
© 2020 Baumert et al.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - In neurons, dendrites form the major sites of information receipt and integration. It is thus vital that, during development, the dendritic arbor is adequately formed to enable proper neural circuit formation and function. While several known processes shape the arbor, little is known of those that govern dendrite branching versus extension. Here, we report a new mechanism instructing dendrites to branch versus extend. In it, glutamate signaling activates mGluR5 receptors to promote Ckd5-mediated phosphorylation of the C-terminal PDZ-binding motif of delta-catenin. The phosphorylation state of this motif determines delta-catenin’s ability to bind either Pdlim5 or Magi1. Whereas the delta:Pdlim5 complex enhances dendrite branching at the expense of elongation, the delta:Magi1 complex instead promotes lengthening. Our data suggest that these complexes affect dendrite development by differentially regulating the small-GTPase RhoA and actin-associated protein Cortactin. We thus reveal a “phospho-switch” within delta-catenin, subject to a glutamate-mediated signaling pathway, that assists in balancing the branching versus extension of dendrites during neural development.
AB - In neurons, dendrites form the major sites of information receipt and integration. It is thus vital that, during development, the dendritic arbor is adequately formed to enable proper neural circuit formation and function. While several known processes shape the arbor, little is known of those that govern dendrite branching versus extension. Here, we report a new mechanism instructing dendrites to branch versus extend. In it, glutamate signaling activates mGluR5 receptors to promote Ckd5-mediated phosphorylation of the C-terminal PDZ-binding motif of delta-catenin. The phosphorylation state of this motif determines delta-catenin’s ability to bind either Pdlim5 or Magi1. Whereas the delta:Pdlim5 complex enhances dendrite branching at the expense of elongation, the delta:Magi1 complex instead promotes lengthening. Our data suggest that these complexes affect dendrite development by differentially regulating the small-GTPase RhoA and actin-associated protein Cortactin. We thus reveal a “phospho-switch” within delta-catenin, subject to a glutamate-mediated signaling pathway, that assists in balancing the branching versus extension of dendrites during neural development.
UR - http://www.scopus.com/inward/record.url?scp=85092679271&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85092679271&partnerID=8YFLogxK
U2 - 10.1083/JCB.201909166
DO - 10.1083/JCB.201909166
M3 - Article
C2 - 33007084
AN - SCOPUS:85092679271
SN - 0021-9525
VL - 219
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 11
M1 - 201909166
ER -