Cc2d1a, a C2 domain containing protein linked to nonsyndromic mental retardation, controls functional maturation of central synapses.

MENG ZHAO ; JESICA RAINGO (CO-PRIMER AUTOR); ZHIJIAN JAMES CHEN; EGE T. KAVALAL

JOURNAL OF NEUROPHYSIOLOGY

AMER PHYSIOLOGICAL SOC

Lugar: Bethesda; Año: 2011 p. 1506 - 1515

0022-3077

Cc2d1a, a C2 domaincontaining protein linked to nonsyndromic mental retardation, controlsfunctional maturation of central synapses. J Neurophysiol 105: 1506–1515,2011. First published January 27, 2011; doi:10.1152/jn.00950.2010.—Cc2d1a is an evolutionarily conserved protein composed of NH2-terminalDrosophila melanogaster 14 domain (DM14) domains and a COOHterminalC2 domain. Human patients with homozygotic mutation in thegene suffer from nonsyndromic mental retardation, implying that Cc2d1afunctions in the central nervous system. To examine the physiologicalrole of the Cc2d1a, we generated and analyzed Cc2d1a knockout (KO)mice. Cc2d1a KO mice die soon after birth, apparently because of theirinability to breathe. Histological analysis of Cc2d1a KO animals did notidentify any structural defects in the peripheral respiratory apparatus.However, functional analysis of synapses formed between Cc2d1adeficientcortical neurons revealed a robust increase in the pace ofmaturation of evoked synaptic responses as well as synaptic vesicletrafficking. This synaptic anomaly was rescued by reintroducing fulllengthCc2d1a but not C2-domain-deletion mutant, underscoring thefunctional importance of C2 domain. Our data suggest that Cc2d1a isrequired for mouse survival and performs essential function in controllingfunctional maturation of synapses.