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Structural origins of clustered protocadherin-mediated neuronal barcoding.


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.

SUBMITTER: Rubinstein R 

PROVIDER: S-EPMC5582985 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Structural origins of clustered protocadherin-mediated neuronal barcoding.

Rubinstein Rotem R   Goodman Kerry Marie KM   Maniatis Tom T   Shapiro Lawrence L   Honig Barry B  

Seminars in cell & developmental biology 20170722


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  ...[more]

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