McPherson Clifton E, Eipper Betty A, Mains Richard E
Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030-3401, USA.
Gene. 2002 Feb 6;284(1-2):41-51. doi: 10.1016/s0378-1119(02)00386-4.
Multidomain guanine nucleotide (GDP/GTP) exchange factor (GEF) proteins coordinate diverse inputs that signal the actin cytoskeleton. Mammals have two such proteins (Kalirin, Trio), while Drosophila has one, which plays essential roles within and outside the nervous system. For Kalirin, numerous isoforms containing different combinations of functional domains are generated through alternative splicing and use of alternative transcriptional start sites. These different isoforms potentially allow a wide variety of proteins to interact with Kalirin, thereby affecting the activity of the functional domains. Humans, like rats, express a large set of Kalirin isoform mRNAs, and we identified a novel Kalirin isoform, containing only the second GEF domain. Kalirin isoforms are predominantly expressed in the brain, while Trio is expressed in a wider variety of tissues. Alternative splicing and transcription of Kalirin are differentially regulated during development in rats and humans, resulting in expression of isoforms of Kalirin containing different functional domains at different times and locations. The prevalence of Kalirin in the cortex throughout life suggests roles in axonal development and the mature brain.
多结构域鸟嘌呤核苷酸（GDP/GTP）交换因子（GEF）蛋白可协调多种输入信号，这些信号作用于肌动蛋白细胞骨架。哺乳动物有两种此类蛋白（卡里林、Trio），而果蝇只有一种，该蛋白在神经系统内外均发挥着重要作用。对于卡里林而言，通过可变剪接和使用可变转录起始位点可产生众多包含不同功能域组合的异构体。这些不同的异构体可能使多种蛋白质与卡里林相互作用，从而影响功能域的活性。与大鼠一样，人类表达大量卡里林异构体mRNA，我们鉴定出一种仅包含第二个GEF结构域的新型卡里林异构体。卡里林异构体主要在大脑中表达，而Trio在多种组织中表达。在大鼠和人类发育过程中，卡里林的可变剪接和转录受到不同调控，导致在不同时间和位置表达包含不同功能域的卡里林异构体。卡里林在整个生命周期的皮质中普遍存在，表明其在轴突发育和成熟大脑中发挥作用。
