COOH-terminal collagen Q (COLQ) mutants causing human deficiency of endplate acetylcholinesterase impair the interaction of ColQ with proteins of the basal lamina.
COOH-terminal collagen Q (COLQ) mutants causing human deficiency of endplate acetylcholinesterase impair the interaction of ColQ with proteins of the basal lamina.
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DOI：
10.1007/s00439-013-1391-3
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发表时间：
2014-05
期刊：
影响因子：
5.3
通讯作者：
Maselli, Ricardo A.
中科院分区：
文献类型：
--
作者：
Arredondo, Juan;Lara, Marian;Ng, Fiona;Gochez, Danielle A.;Lee, Diana C.;Logia, Stephanie P.;Joanna Nguyen;Maselli, Ricardo A.
胶原蛋白Q（ColQ）是神经肌肉接头（NMJ）的一种关键多结构域功能蛋白，对于将乙酰胆碱酯酶（AChE）锚定到基底膜（BL）并在NMJ积累AChE至关重要。AChE与BL的连接主要通过ColQ胶原结构域与硫酸乙酰肝素蛋白聚糖串珠素的结合以及COOH末端与肌肉特异性受体酪氨酸激酶（MuSK）的结合来完成，而后者又在NMJ的发育和维持中起着重要作用。然而，ColQ将AChE锚定在NMJ的确切机制仍然未知。我们确定了五个新的突变在COOH-末端的ColQ在7例患者从5个家庭终板（EP）AChE缺乏症。我们发现这些突变不影响ColQ与AChE的组装以形成AChE的不对称形式或损害ColQ与串珠素的相互作用。相比之下，所有突变都在不同程度上损害ColQ与MuSK的相互作用以及没有可检测到的MuSK的基底膜提取物（BME）。我们的数据证实了ColQ与串珠素和MuSK的相互作用对于将AChE锚定到NMJ是至关重要的。此外，鉴定的COOH-末端突变体不仅减少ColQ与MuSK的相互作用，而且减少ColQ与BME的相互作用。这些研究结果表明，受损的连接的COOH-末端突变体导致EP乙酰胆碱酯酶缺乏症是部分独立的MuSK，和COOH-末端的ColQ可能与其他蛋白质的BL。
Collagen Q (ColQ) is a key multidomain functional protein of the neuromuscular junction (NMJ), crucial for anchoring acetylcholinesterase (AChE) to the basal lamina (BL) and accumulating AChE at the NMJ. The attachment of AChE to the BL is primarily accomplished by the binding of the ColQ collagen domain to the heparan sulfate proteoglycan perlecan and the COOH-terminus to the muscle-specific receptor tyrosine kinase (MuSK), which in turn plays a fundamental role in the development and maintenance of the NMJ. Yet, the precise mechanism by which ColQ anchors AChE at the NMJ remains unknown. We identified five novel mutations at the COOH-terminus of ColQ in seven patients from five families affected with endplate (EP) AChE deficiency. We found that the mutations do not affect the assembly of ColQ with AChE to form asymmetric forms of AChE or impair the interaction of ColQ with perlecan. By contrast, all mutations impair in varied degree the interaction of ColQ to MuSK as well as basement membrane extract (BME) that have no detectable MuSK. Our data confirm that the interaction of ColQ to perlecan and MuSK is crucial for anchoring AChE to the NMJ. In addition, the identified COOH-terminal mutants not only reduce the interaction of ColQ with MuSK, but also diminish the interaction of ColQ with BME. These findings suggest that the impaired attachment of COOH-terminal mutants causing EP AChE deficiency is in part independent of MuSK, and that the COOH-terminus of ColQ may interact with other proteins at the BL.
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影响因子：
5.8
作者：
ELLMAN, GL;COURTNEY, KD;FEATHERSTONE, RM
通讯作者：
FEATHERSTONE, RM
影响因子：
7.8
作者：
Feng, G;Krejci, E;Molgo, J;Cunningham, J M;Massoulie, J;Sanes, J R
通讯作者：
Sanes, J R
DOI：
10.1083/jcb.200206096
发表时间：
2002-10-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Arredondo J;Nguyen VT;Chernyavsky AI;Bercovich D;Orr-Urtreger A;Kummer W;Lips K;Vetter DE;Grando SA
通讯作者：
Grando SA
影响因子：
4.8
作者：
Debnath, J;Muthuswamy, SK;Brugge, JS
通讯作者：
Brugge, JS
影响因子：
11.4
作者：
Dvir, H;Harel, M;Silman, I
通讯作者：
Silman, I