The Role of Geranylgeranyltransferase I-Mediated Protein Prenylation in the Brain

详细信息    查看全文

• 作者：Shangfeng Gao ; Rutong Yu ; Xiuping Zhou
• 关键词：GGTI ; Rac1 ; Dendritogenesis ; Aging ; Alzheimer’s disease ; Multiple sclerosis
• 刊名：Molecular Neurobiology
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：53
• 期：10
• 页码：6925-6937
• 全文大小：5,805 KB
• 刊物主题：Neurosciences; Neurobiology; Cell Biology; Neurology;
• 出版者：Springer US
• ISSN：1559-1182
• 卷排序：53

文摘

Isoprenylation is a posttranslational modification that transfers farnesyl pyrophosphate (FPP) or geranylgeranyl pyrophosphate (GGPP) to cysteine residues of a particular set of proteins, causing their localization to the plasma membrane and other cellular compartments and so rendering them biologically active. Such a modification process, catalyzed by protein prenyltransferase including farnesyltransferase (FT), geranylgeranyltransferase I (GGTI), and geranylgeranyltransferase II (GGTII), is required for the transforming activity of many oncogenic proteins, including some RAS family members. In the past three decades, prenyltransferase has been extensively studied as a promising cancer therapeutic target in vitro, in animal models, and in the clinic. Recently, a growing number of studies suggest that prenyltransferases and the substrates FPP and GGPP also play fundamental roles in nervous system development and brain disorders. However, a systemic review about the advances of prenyltransferases in the field of neuroscience is lacking so far. Herein, we give a brief introduction for the structure and distribution of GGTI and comprehensively updated the recent advances of GGTI in neuronal dendritogenesis/synaptogenesis and in learning/memory-related behavioral performance. More importantly, we discussed the involvement of GGTI and its substrate GGPP in neurodegenerative disorders, such as aging, Alzheimer’s disease, multiple sclerosis, and Niemann-Pick disease type C. The role of FT-FPP and GGTII is mentioned as well to compare with GGTI in these physiological and pathological processes. We hope that this systematical review about what we know about GGTI research in the brain can stimulate further studies on the underlying mechanism of GGTI-mediated isoprenylation in the pathogenesis of neurodegenerative and neurodevelopmental disorders.