Lutz Birnbaumer, Ph.D.
NIH Distinguished Investigator
Neurobiology Laboratory / Transmembrane Signaling Group
Building 101, Room F179
111 T.W. Alexander Drive
Research Triangle Park, NC 27709
- Molecular mechanism by which a G protein coupled receptor (GPCR) activates its cognate heterotrimeric G protein. Although it is well known that GPCRs activate G proteins by promoting the exchange of GTP for GDP, the mechanism by which this comes about is not. We are attempting to co-crystallize the light-activated receptor, rhodopsin, in rod outer segments with its G protein, transducin, in their active conformations. We will prepare a stable constitutively active rhodopsin ñ generated by site directed mutagenesis via homolgous recombination in ES cells ñ and combine the mutated protein purified from stably transfected CHO cells with recombinant transducin prepared by combining transducin α expressed and purified from bacteria with G-βγ expressed and purified from Sf9 insect cells.
- Molecular makeup of the channels that mediate calcium entry into cells responsible for slow Ca signaling as opposed to rapid signaling such as induced by activation of voltage gated calcium channels. The channels mediating slow signaling by calcium ñ which also requires sustained elevation of calcium ñ have been defined as receptor and store operated channels and involve two types of molecules known as Orai and TRPCs. It is a matter of controversy as to whether store operated calcium entry is mediated by channels made up exclusively of Orai molecules or whether both TRPCs and Orai molecules form the entry channels. It is also a matter of discussion whether Orai molecules participate in the phenomenon of receptor operated calcium entry or whether this requires Orai plus TRPCs or TRPCs only. We are testing the molecular basis of store and receptor operated calcium entries, by generating a cell line that is null for all TRPC channels. We have just obtained a cell line expressing only one TRPC in which we are testing the nature of its store operated Ca entry.
- Physiological and pathophysiological roles of TRPCs and non-sensory PTX-sensitive G proteins as seen in KO Mice. We have active collaborations with extramural researchers to study the physiological roles of TRPC channels and G protein α subunits in knockout mice. The mouse knockout colonies are bred here to produce the multiple (double, triple, etc) KOs and to generate strains with conditional KOs.
Ph.D in Biochemistry from the University of Buenos Aires, Argentina, 1966. Postdoctoral training 1967-1971 with Dr. Martin Rodbell at the NIH. Academic appointments at Northwestern University (Associate Professor of Physiology, 1971-1975), Baylor College of Medicine (Professor of Cell Biology, 1975-1994), University of California at Los Angeles (Professor of Anesthesiology, Biological Chemistry and Molecular, Cell and Developmental Biology, 1994-2001). At NIEHS since 2001.
Honors and Awards: CC Bell Research Professorship of Cell Biology (1986-1994), Member of the US National Academy of Sciences (1995), Foreign Member of the Argentine National Academy of Sciences (2004). Foreign Member of the Argentine Academy of Medicine (2006), NIH Distinguished Investigator (2007). Prize "Luis Federico Leloir for International Cooperation in Science, Technology and Innovation" (Argentina, 2011).
Wang Y, Park S, Bajpayee NS, Nagaoka Y, Boulay G, Birnbaumer L, Jiang M. Augmented glucose-induced insulin release in mice lacking G(o2), but not G(o1) or G(i) proteins. Proc Natl Acad Sci U S A. 2011;108(4):1693-8.
Zurita A, Zhang Y, Pedersen L, Darden T, Birnbaumer L. Obligatory role in GTP hydrolysis for the amide carbonyl oxygen of the Mg(2+)-coordinating Thr of regulatory GTPases. Proc Natl Acad Sci U S A. 2010;107(21):9596-601.
Liao Y, Plummer NW, George MD, Abramowitz J, Zhu MX, Birnbaumer L. A role for Orai in TRPC-mediated Ca2+ entry suggests that a TRPC:Orai complex may mediate store and receptor operated Ca2+ entry. Proc Natl Acad Sci U S A. 2009;106(9):3202-6.
Zhu X, Jiang M, Peyton M, Boulay G, Hurst R, Stefani E, Birnbaumer L. trp, a novel mammalian gene family essential for agonist-activated capacitative Ca2+ entry. Cell. 1996;85(5):661-71.
Rudolph U, Finegold MJ, Rich SS, Harriman GR, Srinivasan Y, Brabet P, Boulay G, Bradley A, Birnbaumer L. Ulcerative colitis and adenocarcinoma of the colon in G alpha i2-deficient mice. Nat Genet. 1995;10(2):143-50.