A few recent publications from Mark von Zastrow’s Lab:
1) Puthenveedu, M., Lauffer, B., Temkin, P., Vistein, R., Carlton, P., Thorn, K., Taunton, J., Weiner, O. D., Parton, R. G. , & von Zastrow, M. (2010) Sequence-dependent sorting of recycling proteins by actin-stabilized endosomal microdomains. Cell, 143(5), 761-73, PMID: 2111123.
This study describes a particular type of membrane tubule that is responsible for delivering catecholamine receptors to the surface of cells. It also proposes a new biophysical principle for how receptors get 'sorted' between recycling and degradative fates after endocytosis induced by native ligands or drugs. This is a key cellular decision that determines whether activation of neurotransmitter receptors mediates sustained signaling or a transient response limited by the process of receptor down-regulation. The first author, formerly a postdoctoral fellow in the von Zastrow laboratory, is presently directing his independent research laboratory as an Assistant Professor of Biology at Carnegie Mellon University. The study includes collaborative input from several UCSF colleagues (Cardiovascular Research Institute, Department of Biochemistry and Biophysics, and Department of Cellular & Molecular Pharmacology), as well as a colleague in Australia (Institute of Molecular Bioscience, University of Queensland).
2) Henry, A. G., White, I. J., Marsh, M., von Zastrow, M., & Hislop, J. (2010) The role of ubiquitination in lysosomal trafficking of opioid receptors. Traffic (in press), PMID: 21106040.
This study delineates the sequence of events that mediate down-regulation of opioid receptors in response to prolonged or repeated activation. It shows that ubiquitin, a polypeptide linked to the receptor by enzyme-mediated isopeptide bind formation, plays a specific role in directing receptors from the surface membrane to interior of a specialized multilayered membrane compartment; this is a 'staging area' from which receptors are rapidly destroyed. The first author of this article is a graduate student in the UCSF Cell Biology Program. The last author is a senior postdoctoral scientist in the von Zastrow laboratory, and is appointed as a Specialist in the Department of Psychiatry at UCSF. The study includes collaborative input from colleagues at the MRC Laboratory for Molecular Cell Biology in London (University College).
3) Tzingounis, A. V., von Zastrow, M., Yudowski, G. A. (2010) Beta-blocker drugs mediate calcium signaling in native central nervous system neurons by arrestin–biased agonism. Proceedings of the National Academy of Sciences (in press), PMID: 21078978.
This study describes a new signaling mechanism, biochemically distinct from that elicited by catecholamine, by which a limited subset of beta-blocker drugs regulate calcium signaling in neurons upon binding to the beta-2 adrenergic catecholamine receptor. The study builds on a developing body of research supporting the concept of 'ligand bias' or 'functional selectivity' as a new principle of drug action. It also provides a possible mechanism for understanding neuropsychiatric effects of beta-blocker drugs that cannot be explained by the classical view of these drugs as simple antagonists of norepinephrine. The first and last authors, formerly postdoctoral fellows, are now independent investigators (both Assistant Professors) in the Department of Physiology and Neurobiology, University of Connecticut (first author) and Institute of Neurobiology, University of Puerto Rico (last author).