Kalrn plays key roles within and outside of the nervous system.
Kalrn plays key roles within and outside of the nervous system.
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DOI：
10.1186/1471-2202-13-136
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发表时间：
2012-11-01
期刊：
影响因子：
2.4
通讯作者：
Mains RE
中科院分区：
文献类型：
--
作者：
Mandela P;Yankova M;Conti LH;Ma XM;Grady J;Eipper BA;Mains RE
人类 KALRN 基因编码复杂的多功能 Rho GDP/GTP 交换因子，与心血管疾病、精神疾病和神经退行性疾病有关。对现有 Kalrn 敲除小鼠模型的检查仅集中于神经元表型。然而，Kalirin 最初是通过其与参与多种生物活性肽的合成和分泌的酶的相互作用而被识别的，并且对秀丽隐杆线虫的研究揭示了其直系同源物在神经分泌中的作用。我们使用了广泛的测试来评估消除 Kalrn (KalSRKO/KO) 血影蛋白重复区域中单个外显子的影响；编码仅包含第二个 GEF 结构域的 Kalrn 亚型的转录物仍然可以从单个剩余的功能性 Kalrn 启动子产生。正如预期的那样，KalSRKO/KO 小鼠表现出焦虑样行为减少和被动回避缺陷。在声惊吓的前脉冲抑制或抑郁样行为的测试中没有观察到变化。 KalSRKO/KO 小鼠的生长速度、分娩以及生长激素和催乳素的垂体分泌不足。基于 Kalrn 亚型的一个子集在小鼠骨骼肌中表达的事实以及秀丽隐杆线虫的肌肉功能需要其 Kalrn 直系同源物的观察，在旋转杆和钢丝悬挂测试中对 KalSRKO/KO 小鼠进行了评估。 KalSRKO/KO 小鼠的神经肌肉功能显着下降，其中 KalSR+/KO 小鼠的缺陷明显；当 Kalrn 表达缺失仅限于神经系统时，这些缺陷并不那么明显。观察到神经肌肉接头的突触前和突触后缺陷，以及肌节长度的改变。当 Kalrn 表达被消除时，在神经系统内外观察到的许多广泛且多样化的缺陷可能反映了其在分泌颗粒功能中的作用及其在神经系统外的表达。
The human KALRN gene, which encodes a complex, multifunctional Rho GDP/GTP exchange factor, has been linked to cardiovascular disease, psychiatric disorders and neurodegeneration. Examination of existing Kalrn knockout mouse models has focused only on neuronal phenotypes. However, Kalirin was first identified through its interaction with an enzyme involved in the synthesis and secretion of multiple bioactive peptides, and studies in C.elegans revealed roles for its orthologue in neurosecretion. We used a broad array of tests to evaluate the effects of ablating a single exon in the spectrin repeat region of Kalrn (KalSRKO/KO); transcripts encoding Kalrn isoforms containing only the second GEF domain can still be produced from the single remaining functional Kalrn promoter. As expected, KalSRKO/KO mice showed a decrease in anxiety-like behavior and a passive avoidance deficit. No changes were observed in prepulse inhibition of acoustic startle or tests of depression-like behavior. Growth rate, parturition and pituitary secretion of growth hormone and prolactin were deficient in the KalSRKO/KO mice. Based on the fact that a subset of Kalrn isoforms is expressed in mouse skeletal muscle and the observation that muscle function in C.elegans requires its Kalrn orthologue, KalSRKO/KO mice were evaluated in the rotarod and wire hang tests. KalSRKO/KO mice showed a profound decrease in neuromuscular function, with deficits apparent in KalSR+/KO mice; these deficits were not as marked when loss of Kalrn expression was restricted to the nervous system. Pre- and postsynaptic deficits in the neuromuscular junction were observed, along with alterations in sarcomere length. Many of the widespread and diverse deficits observed both within and outside of the nervous system when expression of Kalrn is eliminated may reflect its role in secretory granule function and its expression outside of the nervous system.
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DOI：
10.1083/jcb.6.1.7
发表时间：
1959-08
期刊：
The Journal of biophysical and biochemical cytology
影响因子：
--
作者：
DE HARVEN E;COERS C
通讯作者：
COERS C
影响因子：
4.8
作者：
DICKERSON, IM;MAINS, RE
通讯作者：
MAINS, RE
影响因子：
11
作者：
Hill, J. J.;Hashimoto, T.;Lewis, D. A.
通讯作者：
Lewis, D. A.
DOI：
10.1073/pnas.0904636106
发表时间：
2009-08-04
影响因子：
11.1
作者：
Cahill, Michael E.;Xie, Zhong;Penzes, Peter
通讯作者：
Penzes, Peter
影响因子：
4.4
作者：
Beresewicz, Malgorzata;Kowalczyk, Joanna E.;Zablocka, Barbara
通讯作者：
Zablocka, Barbara