SynGAP splice variants display heterogeneous spatio-temporal expression and subcellular distribution in the developing mammalian brain.
SynGAP splice variants display heterogeneous spatio-temporal expression and subcellular distribution in the developing mammalian brain.
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DOI：
10.1111/jnc.14988
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发表时间：
2020-09
影响因子：
4.7
通讯作者：
Bayés À
中科院分区：
文献类型：
--
作者：
Gou G;Roca-Fernandez A;Kilinc M;Serrano E;Reig-Viader R;Araki Y;Huganir RL;de Quintana-Schmidt C;Rumbaugh G;Bayés À
The SynGAP protein is a major regulator of synapse biology and neural circuit function. Genetic variants linked to epilepsy and intellectual disability disrupt synaptic function and neural excitability. SynGAP has been involved in multiple signaling pathways and can regulate small GTPases with very different roles. Yet, the molecular bases behind this pleiotropy are poorly understood. We hypothesize that different SynGAP isoforms will mediate different sets of functions and that deciphering their spatio‐temporal expression and subcellular localization will accelerate understanding their multiple functions. Using isoform‐specific antibodies recognizing SynGAP in mouse and human samples we found distinctive developmental expression patterns for all SynGAP isoforms in five mouse brain areas. Particularly noticeable was the delayed expression of SynGAP‐α1 isoforms, which directly bind to postsynaptic density‐95, in cortex and hippocampus during the first 2 weeks of postnatal development. Suggesting that during this period other isoforms would have a more prominent role. Furthermore, we observed subcellular localization differences between isoforms, particularly throughout postnatal development. Consistent with previous reports, SynGAP was enriched in the postsynaptic density in the mature forebrain. However, SynGAP was predominantly found in non‐synaptic locations in a period of early postnatal development highly sensitive to SynGAP levels. While, α1 isoforms were always found enriched in the postsynaptic density, α2 isoforms changed from a non‐synaptic to a mostly postsynaptic density localization with age and β isoforms were always found enriched in non‐synaptic locations. The differential expression and subcellular distribution of SynGAP isoforms may contribute to isoform‐specific regulation of small GTPases, explaining SynGAP pleiotropy. Syngap1 gene encodes for different synaptic Ras/Rap GTPase‐activating (SynGAP) isoforms which are key for brain function. SynGAP C‐termini splice variants show different spatio‐temporal expression and subcellular localization in the developing mouse brain. This study reveals a non‐synaptic and heterogenous role of SynGAP spliced variants. Depicted abundance differences only allow relative comparison within a given tissue (top panel), postnatal age (PND, middle panel), or subcellular distribution (bottom panel). Ctx, cortex; Hip, hippocampus; Str, striatum; OB, Olfactory Bulb; Crb, cerebellum and tSynGAP, total SynGAP.
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影响因子：
16.6
作者：
通讯作者：
--
DOI：
10.1016/j.mcn.2018.03.008
发表时间：
2018-09
期刊：
Molecular and cellular neurosciences
影响因子：
--
作者：
Kilinc M;Creson T;Rojas C;Aceti M;Ellegood J;Vaissiere T;Lerch JP;Rumbaugh G
通讯作者：
Rumbaugh G
影响因子：
14.9
作者：
Bernhofer M;Goldberg T;Wolf S;Ahmed M;Zaugg J;Boden M;Rost B
通讯作者：
Rost B
SYNGAP1 杂合性通过减少体感皮层回路内与触摸相关的活动来破坏感觉处理。
影响因子：
25
作者：
Michaelson SD;Ozkan ED;Aceti M;Maity S;Llamosas N;Weldon M;Mizrachi E;Vaissiere T;Gaffield MA;Christie JM;Holder JL Jr;Miller CA;Rumbaugh G
通讯作者：
Rumbaugh G
影响因子：
5.3
作者：
Clement, James P.;Ozkan, Emin D.;Rumbaugh, Gavin
通讯作者：
Rumbaugh, Gavin