Khanna Rajesh, Wilson Sarah M, Brittain Joel M, Weimer Jill, Sultana Rukhsana, Butterfield Allan, Hensley Kenneth
Program in Medical Neurosciences, Paul & Carole Stark Neurosciences Research Institute Indianapolis, IN 46202, USA ; Departments of Pharmacology & Toxicology, Indianapolis, IN 46202, USA ; Biochemistry & Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA ; Sophia Therapeutics LLC, Indianapolis, IN 46202, USA.
Future Neurol. 2012 Nov 1;7(6):749-771. doi: 10.2217/FNL.12.68.
CRMP2, also known as DPYSL2/DRP2, Unc-33, Ulip or TUC2, is a cytosolic phosphoprotein that mediates axon/dendrite specification and axonal growth. Mapping the CRMP2 interactome has revealed previously unappreciated functions subserved by this protein. Together with its canonical roles in neurite growth and retraction and kinesin-dependent axonal transport, it is now known that CRMP2 interacts with numerous binding partners to affect microtubule dynamics; protein endocytosis and vesicular cycling, synaptic assembly, calcium channel regulation and neurotransmitter release. CRMP2 signaling is regulated by post-translational modifications, including glycosylation, oxidation, proteolysis and phosphorylation; the latter being a fulcrum of CRMP2 functions. Here, the putative roles of CRMP2 in a panoply of neurodegenerative, sensory and motor neuron, and central disorders are discussed and evidence is presented for therapeutic strategies targeting CRMP2 functions.
CRMP2，也被称为DPYSL2/DRP2、Unc-33、Ulip或TUC2，是一种胞质磷蛋白，介导轴突/树突的特化和轴突生长。绘制CRMP2相互作用组图谱揭示了该蛋白以前未被认识到的功能。除了其在神经突生长和回缩以及驱动蛋白依赖性轴突运输中的经典作用外，现在已知CRMP2与众多结合伙伴相互作用以影响微管动力学；蛋白质内吞作用和囊泡循环、突触组装、钙通道调节和神经递质释放。CRMP2信号传导受翻译后修饰的调节，包括糖基化、氧化、蛋白水解和磷酸化；后者是CRMP2功能的关键。在此，讨论了CRMP2在一系列神经退行性、感觉和运动神经元以及中枢疾病中的假定作用，并提供了针对CRMP2功能的治疗策略的证据。
