卡里林调节皮质棘突形态发生和疾病相关行为表型。
Kalirin regulates cortical spine morphogenesis and disease-related behavioral phenotypes.
作者信息
Cahill Michael E, Xie Zhong, Day Michelle, Photowala Huzefa, Barbolina Maria V, Miller Courtney A, Weiss Craig, Radulovic Jelena, Sweatt J David, Disterhoft John F, Surmeier D James, Penzes Peter
机构信息
Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
出版信息
Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):13058-63. doi: 10.1073/pnas.0904636106. Epub 2009 Jul 22.
Dendritic spine morphogenesis contributes to brain function, cognition, and behavior, and is altered in psychiatric disorders. Kalirin is a brain-specific guanine-nucleotide exchange factor (GEF) for Rac-like GTPases and is a key regulator of spine morphogenesis. Here, we show that KALRN-knockout mice have specific reductions in cortical, but not hippocampal, Rac1 signaling and spine density, and exhibit reduced cortical glutamatergic transmission. These mice exhibit robust deficits in working memory, sociability, and prepulse inhibition, paralleled by locomotor hyperactivity reversible by clozapine in a kalirin-dependent manner. Several of these deficits are delayed and age-dependent. Our study thus links spine morphogenic signaling with age-dependent, delayed, disease-related phenotypes, including cognitive dysfunction.
树突棘形态发生有助于大脑功能、认知和行为，且在精神疾病中会发生改变。卡里林是一种针对Rac样GTP酶的脑特异性鸟嘌呤核苷酸交换因子（GEF），是树突棘形态发生的关键调节因子。在此，我们表明KALRN基因敲除小鼠的皮质（而非海马体）Rac1信号传导和树突棘密度有特异性降低，并表现出皮质谷氨酸能传递减少。这些小鼠在工作记忆、社交能力和前脉冲抑制方面表现出明显缺陷，同时伴有氯氮平以卡里林依赖的方式可逆的运动性多动。其中一些缺陷是延迟出现且与年龄相关的。因此，我们的研究将树突棘形态发生信号与年龄依赖性、延迟性、疾病相关表型（包括认知功能障碍）联系起来。
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