Our research concerns membrane physiology in the immune system, neurons and algae, yes, algae, with a focus on SOCE, potassium channels and ABC-type transporters. One current interest is Pavlovian conditioning of allergic reactions, which normally are initiated when mast cells detect multivalent allergens via their FcεRI receptor for Immunoglobulin E (IgE). Allergic rhinitis and other forms of hypersensitivity also can be classically conditioned by IgE-independent stimuli, e.g., nonallergenic odorants. We wish to identify the route of delivery and nature of the signal, by which the nervous system controls mast cell responses to conditioned stimuli. Some evidence points to a contribution of mast cell P2Y receptors, which years ago we showed to mediate chemotaxis, G protein-coupled K+channels, and IgE-linked secretion of inflammatory mediators. In brain progenitors, we determined the developmental expression of Kv channel subtypes during neuronal differentiation, and found that beta subunits previously thought to be neuronally restricted, are present and functional in undifferentiated progenitors. In the green algae Chlamydomonas, HLA3 is a putative bicarbonate transporter of the ABC type, similar in sequence to the CFTR. Our mutational analysis provided direct evidence for ATP dependent transport of bicarbonate by HLA3, per se, in mammalian expression systems. Two of our previous contributions to mast cell biology were to demonstrate that CRAC channels mediate FcεRI-driven Ca2+ influx, and that the NF-AT transcription factor, which until then was thought to be active only in lymphocytes, is activated in mast cells by the FcεRI-triggered calcium influx. Biophysical problems we have addressed include the role of polyisoprenoid lipid mobility in glycosylation reactions, external constraints on lateral diffusion of the FcεRI, and the mechanism by which the attack complex of complement permeabilizes membranes.
Dr. Michael A McCloskey
Area of Expertise:
B.S., Plant Science, University of California-Riverside, 1974
Ph.D., Biochemistry, University of California-Davis, 1979