Functions of the neuron-specific protein ADAP1 (centaurin-α1) in neuronal differentiation and neurodegenerative diseases, with an overview of structural and biochemical properties of ADAP1

Author:

Stricker Rolf,Reiser Georg

Abstract

Abstract Eukaryotic cells express numerous ArfGAPs (ADP-ribosylation factor GTPase-activating proteins). There is increasing knowledge about the function of the brain-specific protein ADAP1 [ArfGAP with dual pleckstrin homology (PH) domain] as well as about its biochemical properties. The ADAP subfamily, also designated centaurin-α, has an N-terminal ArfGAP domain followed by two PH domains. The mammalian ADAP subfamily consists of two identified isoforms, ADAP1 and ADAP2 (centaurin-α1 and -α2). ADAP1 is highly expressed in neurons. We highlight the functional roles of ADAP1 in neuronal differentiation and neurodegeneration. Because of interactions with different proteins and phosphoinositol-lipids, ADAP1 can function as a scaffolding protein in several signal transduction pathways. Firstly, ADAP1 mediates cytoskeletal crosstalk. This is indicated by multiple interactions of ADAP1 with components of the actin and microtubule cytoskeleton. Secondly, regulation of neuronal polarity formation and axon specification by ADAP1 is suggested by crystal structural data obtained for human ADAP1, and the complexes of ADAP1-Ins(1,3,4,5)P4 and/or the forkhead-associated domain of the kinesin KIF13B. These structures support the concept that a KIF13B-ADAP1 complex enhances the local accumulation of PtdIns(3,4,5)P3 at the tips of neurites, and thus favors neuronal polarity. Thirdly, recent evidence unravels a pathological role of ADAP1 because upregulation of ADAP1 by amyloid β-peptide causes ADAP1-Ras-ERK-dependent translocation of Elk-1 to mitochondria. This impairs mitochondrial functions with subsequent synaptic dysfunction and exacerbates neurodegeneration, as in Alzheimer’s disease.

Publisher

Walter de Gruyter GmbH

Subject

Clinical Biochemistry,Molecular Biology,Biochemistry

Reference226 articles.

1. Nuclear shuttling of the peptidase nardilysin;Ma;Arch Biochem Biophys,2004

2. a novel interaction partner of the brain - specific protein IP centaurin α;Haase;Neurochem,2008

3. binding protein nucleolin in disease;Abdelmohsen;RNA RNA Biol,2012

4. Diverse roles of the scaffolding protein;Suresh;Drug Discov Today,2012

5. Structural and functional analysis of the ARFGAP complex reveals a role for coatomer in GTP hydrolysis;Goldberg;Cell,1999

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3