期刊
JOURNAL OF CELL SCIENCE
卷 126, 期 24, 页码 5681-5691出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.134825
关键词
Forward-traffic motifs; Lymphocytes; Neurons; Plasma membrane; Voltage-dependent K+ channels
类别
资金
- Ministerio de Economia y Competitividad (MINECO), Spain [BFU2011-23268, BFU2009-08346, PROMETEO2010/046, CSD2008-00005]
- MINECO
- Juan de la Cierva program (MINECO)
Impairment of Kv1.3 expression at the cell membrane in leukocytes and sensory neuron contributes to the pathophysiology of autoimmune diseases and sensory syndromes. Molecular mechanisms underlying Kv1.3 channel trafficking to the plasma membrane remain elusive. We report a novel non-canonical di-acidic signal (E483/484) at the C-terminus of Kv1.3 essential for anterograde transport and surface expression. Notably, homologous motifs are conserved in neuronal Kv1 and Shaker channels. Biochemical analysis revealed interactions with the Sec24 subunit of the coat protein complex II. Disruption of this complex retains the channel at the endoplasmic reticulum. A molecular model of the Kv1.3-Sec24a complex suggests salt-bridges between the di-acidic E483/484 motif in Kv1.3 and the di-basic R750/752 sequence in Sec24. These findings identify a previously unrecognized motif of Kv channels essential for their expression on the cell surface. Our results contribute to our understanding of how Kv1 channels target to the cell membrane, and provide new therapeutic strategies for the treatment of pathological conditions.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据