Rabaptin-5 regulates receptor expression and functional activation in mast cells.
Rab5 is a small GTPase that regulates early endocytic events and is activated by RabGEF1/Rabex-5. Rabaptin-5, a Rab5 interacting protein, was identified as a protein critical for potentiating RabGEF1/Rabex-5's activation of Rab5. Using Rabaptin-5 shRNA knockdown, we show that Rabaptin-5 is dispensable for Rab5-dependent processes in intact mast cells, including high affinity IgE receptor (FcepsilonRI) internalization and endosome fusion. However, Rabaptin-5 deficiency markedly diminished expression of FcepsilonRI and beta1 integrin on the mast cell surface by diminishing receptor surface stability. This in turn reduced the ability of mast cells to bind IgE and significantly diminished both mast cell sensitivity to antigen (Ag)-induced mediator release and Ag-induced mast cell adhesion and migration. These findings show that, although dispensable for canonical Rab5 processes in mast cells, Rabaptin-5 importantly contributes to mast cell IgE-dependent immunologic function by enhancing mast cell receptor surface stability.
Rios
Eon J
EJ
Department of Pathology, Stanford University School of Medicine, CA, USA.
Piliponsky
Adrian M
AM
Ra
Chisei
C
Kalesnikoff
Janet
J
Galli
Stephen J
SJ
D000818:Animals; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D004705:Endocytosis / Q000235:genetics / Q000276:immunology; D011992:Endosomes / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019012:Integrin beta1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics; D017455:Receptors, IgE / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D000941:Antigens; D020662:Guanine Nucleotide Exchange Factors; D019012:Integrin beta1; D034741:RNA, Small Interfering; C510870:RabGEF1 protein, mouse; C486276:Rabep1 protein, mouse; D017455:Receptors, IgE; D033921:Vesicular Transport Proteins; D020696:rab5 GTP-Binding Proteins