PMID- 25947911
OWN - NLM
STAT- MEDLINE
DCOM- 20160519
LR  - 20181217
IS  - 1347-5215 (Electronic)
IS  - 0918-6158 (Linking)
VI  - 38
IP  - 5
DP  - 2015
TI  - GTP- and GDP-Dependent Rab27a Effectors in Pancreatic Beta-Cells.
PG  - 663-8
LID - 10.1248/bpb.b14-00886 [doi]
AB  - Small guanosine triphosphatases (GTPases) participate in a wide variety of 
      cellular functions including proliferation, differentiation, adhesion, and 
      intracellular transport. Conventionally, only the guanosine 5'-triphosphate 
      (GTP)-bound small GTPase interacts with effector proteins, and the resulting 
      downstream signals control specific cellular functions. Therefore, the GTP-bound 
      form is regarded as active, and the focus has been on searching for proteins that 
      bind the GTP form to look for their effectors. The Rab family small GTPase Rab27a 
      is highly expressed in some secretory cells and is involved in the control of 
      membrane traffic. The present study reviews recent progress in our understanding 
      of the roles of Rab27a and its effectors in pancreatic beta-cells. In the basal 
      state, GTP-bound Rab27a controls insulin secretion at pre-exocytic stages via its 
      GTP-dependent effectors. We previously identified novel guanosine 5'-diphosphate 
      (GDP)-bound Rab27-interacting proteins. Interestingly, GDP-bound Rab27a controls 
      endocytosis of the secretory membrane via its interaction with these proteins. We 
      also demonstrated that the insulin secretagogue glucose converts Rab27a from its 
      GTP- to GDP-bound forms. Thus, GTP- and GDP-bound Rab27a regulate pre-exocytic 
      and endocytic stages in membrane traffic, respectively. Since the physiological 
      importance of GDP-bound GTPases has been largely overlooked, we consider that the 
      investigation of GDP-dependent effectors for other GTPases is necessary for 
      further understanding of cellular function.
FAU - Yamaoka, Mami
AU  - Yamaoka M
AD  - Department of Pharmacology, Oita University Faculty of Medicine.
FAU - Ishizaki, Toshimasa
AU  - Ishizaki T
FAU - Kimura, Toshihide
AU  - Kimura T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Insulin)
RN  - 0 (rab27 GTP-Binding Proteins)
RN  - 146-91-8 (Guanosine Diphosphate)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - EC 3.6.1.-. (RAB27A protein, human)
RN  - EC 3.6.5.2 (rab GTP-Binding Proteins)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Glucose/metabolism
MH  - Guanosine Diphosphate/*metabolism
MH  - Guanosine Triphosphate/*metabolism
MH  - Humans
MH  - Insulin/*metabolism
MH  - Insulin Secretion
MH  - Insulin-Secreting Cells/*metabolism
MH  - rab GTP-Binding Proteins/*metabolism
MH  - rab27 GTP-Binding Proteins
EDAT- 2015/05/08 06:00
MHDA- 2016/05/20 06:00
CRDT- 2015/05/08 06:00
PHST- 2015/05/08 06:00 [entrez]
PHST- 2015/05/08 06:00 [pubmed]
PHST- 2016/05/20 06:00 [medline]
AID - 10.1248/bpb.b14-00886 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2015;38(5):663-8. doi: 10.1248/bpb.b14-00886.