Structural origins of clustered protocadherin-mediated neuronal barcoding

Rotem Rubinstein, Kerry Marie Goodman, Tom Maniatis, Lawrence Shapiro, Barry Honig

Research output: Contribution to journalReview articlepeer-review

Abstract

Clustered protocadherins mediate neuronal self-recognition and non-self discrimination—neuronal “barcoding”—which underpin neuronal self-avoidance in vertebrate neurons. Recent structural, biophysical, computational, and cell-based studies on protocadherin structure and function have led to a compelling molecular model for the barcoding mechanism. Protocadherin isoforms assemble into promiscuous cis-dimeric recognition units and mediate cell–cell recognition through homophilic trans-interactions. Each recognition unit is composed of two arms extending from the membrane proximal EC6 domains. A cis-dimeric recognition unit with each arm coding adhesive trans homophilic specificity can generate a zipper-like assembly that in turn suggests a chain termination mechanism for self-vs-non-self-discrimination among vertebrate neurons.

Original languageEnglish
Pages (from-to)140-150
Number of pages11
JournalSeminars in Cell and Developmental Biology
Volume69
DOIs
StatePublished - Sep 2017
Externally publishedYes

Keywords

  • Cell-cell recognition
  • Clustered protocadherins
  • Crystal structure
  • Neuronal self-avoidance
  • Protein interaction specificity

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