Ca2+-MYRISTOYL SWITCH IN NEURONAL CALCIUM SENSOR-1: A ROLE OF C-TERMINAL SEGMENTстатья

Статья опубликована в высокорейтинговом журнале

Информация о цитировании статьи получена из Scopus, Web of Science
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 16 июня 2015 г.

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1. Полный текст Baksheeva_2015.pdf 480,6 КБ 23 августа 2016 [zamyat]

[1] Ca2+-myristoyl switch in neuronal calcium sensor-1: A role of c-terminal segment / V. E. Baksheeva, A. A. Nazipova, D. V. Zinchenko et al. // CNS and Neurological Disorders - Drug Targets. — 2015. — Vol. 14, no. 4. — P. 437–451. NCS1 (neuronal calcium sensor-1) is a Ca2+-myristoyl switch protein of the NCS protein family involved in synaptic plasticity and neurotransmission via Ca2+-dependent regulation of dopamine D2 receptor and associated Gprotein coupled receptor kinase (GRK)-2. Overexpression of NCS1 in synaptic terminals results in accumulation of membrane-bound protein and its redundant regulatory activity associated with neurological disorders. Here, we have demonstrated that bovine photoreceptors contain NCS1 that is capable of a partially irreversible interaction with isolated photoreceptor membranes and implicated in Ca2+-dependent binding and regulation of GRK1 in vitro. Using NCS1-recoverin C-terminal chimeric construct (NR), it was found that the Ca2+-myristoyl switch of NCS1 is affected by its C-terminal segment downstream the fourth EF-loop of the protein, which is variable within the NCS family. NR retains structural stability and sensitivity to Ca2+, but interacts with photoreceptor membranes with lower affinity in a Ca2+-dependent fully reversible manner and displays altered GRK1 modulation. These data combined with fluorescent probing of surface hydrophobicity of NCS1, NR and recoverin suggest that the C-terminal segment of NCS1 regulates reuptake of myristoyl group under Ca2+-free conditions and participates in organization of the target-binding pocket of the protein. We point out a putative role of NCS1 in photoreceptors as a modulator of GRK activity and propose targeting of the C-terminal segment of NCS1 as an appropriate way for selective suppression of excessive membrane accumulation and aberrant activity of the protein in neurons associated with central nervous system dysfunctions. [ DOI ]

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