RACK1 has the nerve to act: structure meets function in the nervous system.
The receptor for activated protein kinase C 1 (RACK1) is an intracellular adaptor protein. Accumulating evidence attributes to this member of the tryptophan-aspartate (WD) repeat family the role of regulating several major nervous system pathways. Structurally, RACK1 is a seven-bladed-beta-propeller, interacting with diverse proteins having distinct structural folds. When bound to the IP3 receptor, RACK1 regulates intracellular Ca2+ levels, potentially contributing to processes such as learning, memory and synaptic plasticity. By binding to the NMDA receptor, it dictates neuronal excitation and sensitivity to ethanol. When bound to the stress-induced acetylcholinesterase variant AChE-R, RACK1 is implicated in stress responses and behavior, compatible with reports of RACK1 modulations in brain ageing and in various neurodegenerative diseases. This review sheds new light on both the virtues and the variety of neuronal RACK1 interactions and their physiological consequences.
Sklan
Ella H
EH
The Department of Biological Chemistry, The Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Podoly
Erez
E
Soreq
Hermona
H
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008954:Models, Biological; D008958:Models, Molecular; D009363:Neoplasm Proteins / Q000737:chemistry / Q000502:physiology*; D009420:Nervous System / Q000166:cytology* / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism; D017434:Protein Structure, Tertiary; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology
D015220:Calcium Channels; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D009363:Neoplasm Proteins; C419368:RACK1 protein, human; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D002118:Calcium