Analyses of class II ARF family proteins

2016 Fiscal Year Final Research Report

• Project/Area Number: 25430061
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Gunma University
• Principal Investigator: Sadakata Tetsushi 群馬大学, テニュアトラック普及推進室, 講師 (90391961)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: Tremor

Outline of Final Research Achievements

ADP-ribosylation factors (ARFs) constitute a family of small monomeric GTPases. The ARF family consists of three classes and a total of six members: class I, consisting of ARFs 1-3; class II, consisting of ARFs 4 and 5; and class III, which comprises ARF6. Little is known about the role of the class II ARFs in membrane trafficking. Here, we generated class II ARF knockout mice, and found that ARF4+/-/ARF5-/- mice showed severe tremor. Propranolol and gabapentin, which alleviate symptoms in essential tremor patients, reduced the amplitude of the pathologic tremor. Immunochemical studies showed that Nav1.6 proteins, normally localized in axon initial segment (AIS), was highly decreased in ARF4+/-/ARF5-/- Purkinje cell. These results indicate that the impairment of electrophysiological properties of Purkinje cell by Nav1.6 decrease is related to the onset of pathologic tremor of essential tremor patients.

Free Research Field

神経化学