GTP- and GDP-Dependent Rab27a Effectors in Pancreatic Beta-Cells

Abstract

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.

Coronin1C Is a GDP-Specific Rab44 Effector That Controls Osteoclast Formation by Regulating Cell Motility in Macrophages

“…The present finding that the GDP form of Rab44 interacts with Coronin1C in macrophages and osteoclasts is reminiscent of the previous results of the interaction between the GDP form of Rab27A and Coronin1C in pancreatic β cells [ 19 , 20 ]. During the transport of insulin granules in β cells, the GDP-form of Rab27A controls “endocytosis” by interacting with GDP-form effectors, such as Coronin1C [ 19 ] and IQGAP1 [ 21 ]; however, the GTP-form of Rab27A regulates “exocytosis” by interacting with GTP-form effectors, such as Exophilin8/Slac2-c/MyRIP [ 22 ], Granuphilin/Slp4a [ 23 ], and Exophilin7/JFC1/Slp1 [ 24 ].…”

Transcription Analysis of Liver and Muscle Tissues from Landrace Finishing Pigs with Different Feed Conversion Ratios

“…GTP is an important component of riboflavin (vitamin B2), which is synthesized from GTP and ribose 5-phosphate. As a substrate [ 45 ], GTP also participates in a variety of other biological activities (e.g., proliferation, differentiation, adhesion, and intracellular transport) which promote physiological growth and development and improve FE [ 46 ]. Based on the networks of DEGs, gene ontology, and KEGG pathways, functional genes, such as solute carrier ( SLC ) gene families which contain many glucose transporters, were enriched and considered tumor suppressors [ 47 ].…”

Rab27a Contributes to the Processing of Inflammatory Pain in Mice

“…As we demonstrate that (i) Rab27a protein is expressed to a much higher extend in the spinal cord as compared to DRG neurons, (ii) Rab27a can only be detected on mRNA but not on protein level in DRGs and (iii) Rab27a protein signal is enriched in the superficial dorsal horn of the spinal cord, co-localizing with marker for primary afferent neurons, our data suggest that Rab27a protein in sensory neurons might be transported to central terminals within the spinal cord. As Rab27a is an important regulator of exocytosis processes in various cell types [ 43 , 44 , 45 , 46 , 47 , 48 ], it seems likely that also in the spinal cord Rab27a regulates vesicle transport or vesicle fusion in synaptic terminals of primary afferent neurons.…”