TY - JOUR
T1 - Neuronal function and dysfunction of CYFIP2
T2 - From actin dynamics to early infantile epileptic encephalopathy
AU - Zhang, Yinhua
AU - Lee, Yeunkum
AU - Han, Kihoon
N1 - Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government Ministry of Science and ICT (NRF-2018R1C1B6001235, NRF-2018 R1A6A3A11040508), and by the Brain Research Program through the NRF funded by the Korea government Ministry of Science and ICT (NRF-2015M3C7A1028790, NRF-2018M3 C7A1024603).
Publisher Copyright:
© 2019 by the The Korean Society for Biochemistry and Molecular Biology.
PY - 2019
Y1 - 2019
N2 - The cytoplasmic FMR1-interacting protein family (CYFIP1 and CYFIP2) are evolutionarily conserved proteins originally identified as binding partners of the fragile X mental retardation protein (FMRP), a messenger RNA (mRNA)-binding protein whose loss causes the fragile X syndrome. Moreover, CYFIP is a key component of the heteropentameric WAVE regulatory complex (WRC), a critical regulator of neuronal actin dynamics. Therefore, CYFIP may play key roles in regulating both mRNA translation and actin polymerization, which are critically involved in proper neuronal development and function. Nevertheless, compared to CYFIP1, neuronal function and dysfunction of CYFIP2 remain largely unknown, possibly due to the relatively less well established association between CYFIP2 and brain disorders. Despite high amino acid sequence homology between CYFIP1 and CYFIP2, several in vitro and animal model studies have suggested that CYFIP2 has some unique neuronal functions distinct from those of CYFIP1. Furthermore, recent whole-exome sequencing studies identified de novo hot spot variants of CYFIP2 in patients with early infantile epileptic encephalopathy (EIEE), clearly implicating CYFIP2 dysfunction in neurological disorders. In this review, we highlight these recent investigations into the neuronal function and dysfunction of CYFIP2, and also discuss several key questions remaining about this intriguing neuronal protein.
AB - The cytoplasmic FMR1-interacting protein family (CYFIP1 and CYFIP2) are evolutionarily conserved proteins originally identified as binding partners of the fragile X mental retardation protein (FMRP), a messenger RNA (mRNA)-binding protein whose loss causes the fragile X syndrome. Moreover, CYFIP is a key component of the heteropentameric WAVE regulatory complex (WRC), a critical regulator of neuronal actin dynamics. Therefore, CYFIP may play key roles in regulating both mRNA translation and actin polymerization, which are critically involved in proper neuronal development and function. Nevertheless, compared to CYFIP1, neuronal function and dysfunction of CYFIP2 remain largely unknown, possibly due to the relatively less well established association between CYFIP2 and brain disorders. Despite high amino acid sequence homology between CYFIP1 and CYFIP2, several in vitro and animal model studies have suggested that CYFIP2 has some unique neuronal functions distinct from those of CYFIP1. Furthermore, recent whole-exome sequencing studies identified de novo hot spot variants of CYFIP2 in patients with early infantile epileptic encephalopathy (EIEE), clearly implicating CYFIP2 dysfunction in neurological disorders. In this review, we highlight these recent investigations into the neuronal function and dysfunction of CYFIP2, and also discuss several key questions remaining about this intriguing neuronal protein.
KW - Actin polymerization
KW - Cytoplasmic FMR1-interacting protein 2 (CYFIP2)
KW - Early infantile epileptic encephalopathy (EIEE)
KW - Neuronal synapse
KW - WAVE regulatory complex (WRC)
UR - http://www.scopus.com/inward/record.url?scp=85066456026&partnerID=8YFLogxK
U2 - 10.5483/BMBRep.2019.52.5.097
DO - 10.5483/BMBRep.2019.52.5.097
M3 - Review article
C2 - 30982501
AN - SCOPUS:85066456026
SN - 1976-6696
VL - 52
SP - 304
EP - 311
JO - BMB Reports
JF - BMB Reports
IS - 5
ER -