MaxiK channel partners: physiological impact
MaxiK channel partners: physiological impact
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DOI：
10.1113/jphysiol.2005.098913
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发表时间：
2006-01-01
影响因子：
5.5
通讯作者：
Toro, L
中科院分区：
文献类型：
--
作者：
Lu, R;Alioua, A;Toro, L
大电导、电压和Ca 2+激活的K+通道（MaxiK、BK、BKCa）的基本功能单元是由单个基因Slo编码的孔形成α亚基（MaxiK α）的四聚体，其具有多个交替外显子。根据组织的不同，MaxiK α可以与调节性β亚基（β 1-β 4）结合，增加其功能多样性。由于MaxiK感知并调节膜电压和细胞内Ca 2+，它将细胞兴奋性与细胞信号传导和代谢联系起来。因此，MaxiK是重要身体功能的关键调节剂，如血流，排尿，免疫和神经传递。癫痫伴阵发性运动障碍综合征已被认为是由功能获得性C端突变引起的MaxiK α相关疾病。该通道区域也是一个关键的识别模块，包含MaxiK α与周围信号传导伙伴相互作用的序列，以及其靶向细胞特异性微结构域。越来越多的相互作用蛋白质的列表突出了与MaxiK α的C末端的关联是动态的并且取决于每个细胞环境的可能性。我们推测，由替代外显子决定的C-末端（和细胞内环）的分子多样性可能会以组织特异性的方式调节或创建额外的相互作用位点。一个挑战是解剖MaxiK大分子信号传导复合物在不同的组织和他们的时间协会/解离根据刺激。
The basic functional unit of the large-conductance, voltage- and Ca2+-activated K+ (MaxiK, BK, BKCa) channel is a tetramer of the pore-forming alpha-subunit (MaxiK alpha) encoded by a single gene, Slo, holding multiple alternative exons. Depending on the tissue, MaxiK alpha can associate with modulatory beta-subunits (beta 1-beta 4) increasing its functional diversity. As MaxiK senses and regulates membrane voltage and intracellular Ca2+, it links cell excitability with cell signalling and metabolism. Thus, MaxiK is a key regulator of vital body functions, like blood flow, uresis, immunity and neurotransmission. Epilepsy with paroxysmal dyskinesia syndrome has been recognized as a MaxiK alpha-related disorder caused by a gain-of-function C-terminus mutation. This channel region is also emerging as a key recognition module containing sequences for MaxiK alpha interaction with its surrounding signalling partners, and its targeting to cell-specific microdomains. The growing list of interacting proteins highlights the possibility that associations with the C-terminus of MaxiK alpha are dynamic and depending on each cellular environment. We speculate that the molecular multiplicity of the C-terminus (and intracellular loops) dictated by alternative exons may modulate or create additional interacting sites in a tissue-specific manner. A challenge is the dissection of MaxiK macromolecular signalling complexes in different tissues and their temporal association/dissociation according to the stimulus.