We study the function and regulation of Na transporters in the surface membrane of mammalian cells, recently with a focus on the regulation of transporters by surface membrane turnover via exo- and endocytosis. To so do, we employ innovative electrical and optical methods. Three Na transporters have been of most interest to us; Na/Ca exchangers, Na/K pumps, and Na/H exchangers, all of which can determine the fate of cardiac cells in pathological settings such as ischemia. To improve biophysical and regulatory studies of these mechanisms, we developed 'giant' patch clamp methods and analyzed conformational changes of transport proteins with 1 microsecond resolution. Recently, we refined ion selective electrode methods to measure ion fluxes independent of electrical activity. Along the way, we discovered that phosphatidylinositides are powerful direct regulators of ion transporters and channels. We are now studying nonconventional endocytic processes that become highly activated in response to metabolic stress. We recently disovered that these domain-driven endocytic processes become activated during ischemia/reperfusion of the heart and can rapidly internalize >30% of the sarcolemma. These studies open new pathways to understand dynamics of cell membranes that are highly relevant to states disease that involve metabolic stress.
- Graduate School
- University of Tuebingen , Biology
- Medical School
- University of Tuebingen (1980), Medicine
- Calcium Signaling
- Lipid Signaling
- Membrane transport mechanisms
- Nonconventional endocytic mechanisms
- Palmitoylation of the Na/Ca exchanger cytoplasmic loop controls its inactivation and internalization during stress signaling.
- Reilly L, Howie J, Wypijewski K, Ashford ML, Hilgemann DW, Fuller W FASEB J. 2015 Jul
- Human-induced pluripotent stem cell-derived cardiomyocytes for studies of cardiac ion transporters.
- Fine M, Lu FM, Lin MJ, Moe OW, Wang HR, Hilgemann DW Am. J. Physiol., Cell Physiol. 2013 Jun
- Massive palmitoylation-dependent endocytosis during reoxygenation of anoxic cardiac muscle.
- Lin MJ, Fine M, Lu JY, Hofmann SL, Frazier G, Hilgemann DW Elife 2013 2 0
- Massive endocytosis triggered by surface membrane palmitoylation under mitochondrial control in BHK fibroblasts.
- Hilgemann DW, Fine M, Linder ME, Jennings BC, Lin MJ Elife 2013 2 0
- Massive endocytosis driven by lipidic forces originating in the outer plasmalemmal monolayer: a new approach to membrane recycling and lipid domains.
- Fine M, Llaguno MC, Lariccia V, Lin MJ, Yaradanakul A, Hilgemann DW J. Gen. Physiol. 2011 Feb 137 2 137-54
- Mechanistic analysis of massive endocytosis in relation to functionally defined surface membrane domains.
- Hilgemann DW, Fine M J. Gen. Physiol. 2011 Feb 137 2 155-72
- Massive calcium-activated endocytosis without involvement of classical endocytic proteins.
- Lariccia V, Fine M, Magi S, Lin MJ, Yaradanakul A, Llaguno MC, Hilgemann DW J. Gen. Physiol. 2011 Jan 137 1 111-32
- Steady-state function of the ubiquitous mammalian Na/H exchanger (NHE1) in relation to dimer coupling models with 2Na/2H stoichiometry.
- Fuster D, Moe OW, Hilgemann DW J. Gen. Physiol. 2008 Oct 132 4 465-80
- Dual control of cardiac Na+ Ca2+ exchange by PIP(2): electrophysiological analysis of direct and indirect mechanisms.
- Related Articles, LinksYaradanakul A, Feng S, Shen C, Lariccia V, Lin MJ, Yang J, Kang T M, Dong P, Yin HL, Albanesi JP, Hilgemann DW. The Journal of Physiology June 2007 582 991-1010
- Molecular control of cardiac sodium homeostasis in health and disease.
- Hilgemann DW, Yaradanakul A, Wang Y, Fuster D J. Cardiovasc. Electrophysiol. 2006 May 17 Suppl 1 S47-S56
Honors & Awards
Lievre Research Award for best cardiovascular research, Greater Los Angeles (0)
Established Investigatorship, American Heart Association (0)
Fellow, Japan Society for the Promotion of Science (University of Kyoto) (0)
Young Investigator Award: International Biophysical Society (0)
- Biophysical Society