Regulatory mechanism of mast cell degranulation by the novel Rab protein
Description: Mast cells are responsible for anaphylaxis and allergy. Rab44 is a large Rab GTPase that contains a Rab GTPase domain and some additional N-terminal domains. Here we investigated the role of Rab44 in the physiology of mast cells and in anaphylaxis. Rab44 knockdown impaired degranulation of murine bone-marrow mast cells (BMMCs). Rab44-knockout mice exhibited diminished anaphylaxis, and Rab44-knockout BMMCs showed a decrease in histamine secretion. Confocal microscopic analysis of constitutively active Rab44 mutants showed their partial translocation from lysosomes to the plasma membrane. Treatment with a Ca2+ ionophore also induced the translocation of Rab44 from lysosomes into the plasma membrane and cytosol. Mechanistically, Rab44 interacted with VAMP8, which is a v-SNARE protein, to promote degranulation. Immunohistochemical studies indicated that Rab44 was detectable by only cells in the immune-related tissues, suggesting that it is closely involved in the inflammatory response.
Amount: ¥4,420,000
Funding type: research
Funder scheme: Grant-in-Aid for Scientific Research (C)
Start date: 2018-04-01
End date: 2022-03-31
Investigator: Tomoko Kadowaki
Institution: Nagasaki University
Funded outputs count: 12
Funder award ID: 18K09536
OpenAlex ID: G7275699113