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Park, Joo Min
인지 및 사회성 연구단
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Homer1a regulates Shank3 expression and underlies behavioral vulnerability to stress in a model of Phelan-McDermid syndrome

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Title
Homer1a regulates Shank3 expression and underlies behavioral vulnerability to stress in a model of Phelan-McDermid syndrome
Author(s)
Lin, Raozhou; Learman, Lisa N.; Bangash, M. Ali; Melnikova, Tatiana; Leyder, Erica; Reddy, Sai C.; Naidoo, Nirinjini; Joo Min Park; Savonenko, Alena; Worley, Paul F.
Publication Date
2021-11-16
Journal
CELL REPORTS, v.37, no.7
Publisher
CELL PRESS
Abstract
Mutations of SHANK3 cause Phelan-McDermid syndrome (PMS), and these individuals can exhibit sensitivity to stress, resulting in behavioral deterioration. Here, we examine the interaction of stress with genotype using a mouse model with face validity to PMS. In Shank3(Delta C/+) mice, swim stress produces an altered transcriptomic response in pyramidal neurons that impacts genes and pathways involved in synaptic function, signaling, and protein turnover. Homer1a, which is part of the Shank3-mGluR-N-methyl-D-aspartate (NMDA) receptor complex, is super-induced and is implicated in the stress response because stress-induced social deficits in Shank3(Delta C/+) mice are mitigated in Shank3(Delta C/+);Homer1a(-/-) mice. Several lines of evidence demonstrate that Shank3 expression is regulated by Homer1a in competition with crosslinking forms of Homer, and consistent with this model, Shank3 expression and function that are reduced in Shank3(Delta C/+) mice are rescued in Shank3(Delta C/+);Homer1a(-/-) mice. Studies highlight the interaction between stress and genetics and focus attention on activity-dependent changes that may contribute to pathogenesis.
URI
https://pr.ibs.re.kr/handle/8788114/10743
DOI
10.1016/j.celrep.2021.110014
ISSN
2211-1247
Appears in Collections:
Center for Cognition and Sociality(인지 및 사회성 연구단) > 1. Journal Papers (저널논문)
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