Associate Professor of Ophthalmology &
Cell Biology & Physiology
Division of Ophthalmology
Department of Surgery
Basic Medical Sciences Building, Rm 377
915 Camino de Salud, NE
Albuquerque, NM 87131
Phone: (505) 272-4968
Fax: (505) 272-6029
DDeretic@salud.unm.edu
Research Interests
Our research focuses on membrane trafficking in retinal photoreceptor cells. This process involves synthesis, sorting and transport, through the rod inner segments (RIS), of prodigious quantity of rhodopsin-laden membranes. They continuously renew specialized organelles filled with light sensitive disk membranes, the rod outer segments (ROS) (see the diagram of the photoreceptor cell).
A significant number of genetic disorders affecting the retina result in altered membraneane only in the proximity of the connecting cilium (C). Newly synthesized membranes are then delivered to trafficking in photoreceptor cells by interfering with rhodopsin transport and ROS morphogenesis and renewal. Several categories of disease-causing mutations have been identified in rhodopsin, and in proteins that regulate intracellular trafficking. Our goal is to better understand how the mutations causing retinal diseases interfere with cellular processes.
We have developed a retinal cell-free system that reconstitutes rhodopsin trafficking in vitro, and established that rhodopsin C-terminal amino acids QVS(A)PA comprise a sorting motif that regulates budding of rhodopsin transport carriers (RTCs). We recently found that membrane lipids, particularly phosphoinositides, regulate RTC budding and their fusion with the RIS plasma membrane. We identified phosphoinositide-binding proteins evectin-1 and ezrin/moesin, which may be recruited by membrane lipids to regulate rhodopsin trafficking. Our recent data suggest that phosphoinositides, moesin, actin and the small GTPases rac1 and rab8 regulate tethering and fusion of RTCs with the RIS plasma membrane. Our studies are currently focused on delineating the molecular interactions between these components, which control the critical steps in the biogenesis of the light-detecting organelle and are therefore essential for photoreceptor health and maintenance of vision.
Education, Honors and Professional Experience
Ph.D. 1992 Biochemistry and Molecular Biology. University of Belgrade; 1991-1996, Assistant Professor, Department of Pathology, University of Texas Health Science Center at San Antonio; 1996-2001 Assistant Professor, Department of Ophthalmology and Visual Sciences, and Department of Cell and Developmental Biology, The University of Michigan, Ann Arbor.
Selected Recent Publications
Deretic D, Schmerl S, Hargrave PA, Arendt A and McDowell JH. (1998) Regulation of sorting and post-Golgi trafficking of rhodopsin by its C-terminal sequence QVS(A)PA. Proc. Natl. Acad. Sci. USA. 95:10620-10625.
Krappa R, Nguyen A, Burrola P, Deretic D and Lemke G. (1999) Evectins: Novel vesicular proteins that carry a plekstrin homology domain and localize to post-Golgi membranes. Proc. Natl. Acad. Sci. USA. 96:4633-4638.
Deretic D. (2000) Rhodopsin trafficking in photoreceptors using retinal cell-free system. In: Vertebrate Phototransduction and the Visual Cycle. Palczewski K, ed., Methods in Enzymology.
J. N. Abelson and M. I. Simon, Ed in Chief. Academic Press, San Diego, CA. 315: 77-88.
Morel V, Poschet R, Traverso V and Deretic D. (2000) Towards the proteome of the rhodopsin-bearing post-Golgi compartment of retinal photoreceptor cells. Electrophoresis, special issue on “Organelle Proteomics”. 21:3460-3469.
Moritz OL, Tam BM, Hurd L, Peranen J, Deretic D and Papermaster DS. (2001) Mutant rab8 impairs docking and fusion of rhodopsin-bearing post-Golgi membranes and causes cell death in transgenic Xenopus rods. Mol. Biol. Cell. 12:2341-2351.
Traverso V, Bush RA, Sieving PA and Deretic D. (2002) Retinal cAMP levels during the progression of retinal degeneration in rhodopsin P23H and S334ter transgenic rats. Invest. Ophthalmol. Vis. Sci. 43:1655-1661.
Deretic D, Traverso V, Parkins N, Jackson F, Rodriguez de Turco EB and Ransom, N. (2004) Phosphoinositides, ezrin/moesin and rac1 regulate fusion of rhodopsin transport carriers in retinal photoreceptors. Mol. Biol. Cell. 15:359-370.
Deretic D, Williams AH, Ransom N, Morel V, Hargrave PA and Arendt A.(2005) Rhodopsin C terminus, the site of mutations causing retinal disease, regulates trafficking by binding to ADP-ribosylation factor 4 (ARF4). Proc. Natl. Acad. Sci. USA. 102:3301-3306.
