Ubiquitination of the protocadherin-γA3 variable cytoplasmic domain modulates cell-cell interaction

Frontiers in Cell and Developmental Biology

Cell and Developmental Biology

Emily Schnall¹  Aliya Mambetalieva¹  Mike Bucaro¹  Nicole LaMassa²  Albert Ptashnik²  Greg R. Phillips³ 

[1] Department of Biology, College of Staten Island, City University of New York, New York, NY, United States;Department of Biology, College of Staten Island, City University of New York, New York, NY, United States;PhD Program in Biology, Subprogram in Neuroscience, CUNY Graduate Center, New York, NY, United States;Department of Biology, College of Staten Island, City University of New York, New York, NY, United States;PhD Program in Biology, Subprogram in Neuroscience, CUNY Graduate Center, New York, NY, United States;Center for Developmental Neuroscience, College of Staten Island, City University of New York, New York, NY, United States;

关键词: endosome;    cell adhesion;    self-avoidance;    endocytosis;    pseudophosphorylation;   

DOI  :  10.3389/fcell.2023.1261048

 received in 2023-07-18, accepted in 2023-09-04,  发布年份 2023

来源: Frontiers

【 摘 要 】

The family of ∼60 clustered protocadherins (Pcdhs) are cell adhesion molecules encoded by a genomic locus that regulates expression of distinct combinations of isoforms in individual neurons resulting in what is thought to be a neural surface “barcode” which mediates same-cell interactions of dendrites, as well as interactions with other cells in the environment. Pcdh mediated same-cell dendrite interactions were shown to result in avoidance while interactions between different cells through Pcdhs, such as between neurons and astrocytes, appear to be stable. The cell biological mechanism of the consequences of Pcdh based adhesion is not well understood although various signaling pathways have been recently uncovered. A still unidentified cytoplasmic regulatory mechanism might contribute to a “switch” between avoidance and adhesion. We have proposed that endocytosis and intracellular trafficking could be part of such a switch. Here we use “stub” constructs consisting of the proximal cytoplasmic domain (lacking the constant carboxy-terminal domain spliced to all Pcdh-γs) of one Pcdh, Pcdh-γA3, to study trafficking. We found that the stub construct traffics primarily to Rab7 positive endosomes very similarly to the full length molecule and deletion of a substantial portion of the carboxy-terminus of the stub eliminates this trafficking. The intact stub was found to be ubiquitinated while the deletion was not and this ubiquitination was found to be at non-lysine sites. Further deletion mapping of the residues required for ubiquitination identified potential serine phosphorylation sites, conserved among Pcdh-γAs, that can reduce ubiquitination when pseudophosphorylated and increase surface expression. These results suggest Pcdh-γA ubiquitination can influence surface expression which may modulate adhesive activity during neural development.

【 授权许可】

Unknown   
Copyright © 2023 Ptashnik, LaMassa, Mambetalieva, Schnall, Bucaro and Phillips.