Christopher Stipp, Ph.D.
        Assistant Professor of Biology and
        Molecular Physiology & Biophysics

Office: Lab: Phone: Lab: FAX: Email:

338 Biology Building East 331 Biology Building East (319) 335-0192 (319) 335-0273 (319) 335-1069 christopher-stipp@uiowa.edu

Research Interests

Cues in the extracellular microenvironment govern the behavior of migrating cells by triggering changes in migration speed or direction. The cell surface receptors that interpret these cues engage cytoplasmic partners to transduce signals, but recent work reveals that many receptors also interact with cell surface proteins that can be critical for proper receptor function. Thus, a more sophisticated understanding of cell migration will require a "cell surface interaction map" describing the connectivity of receptors and their cell surface partners.

To begin to build such an interaction map, we are studying members of the tetraspanin family of cell surface adaptor proteins. Tetraspanins organize complexes containing integrins (major receptors for extracellular matrix proteins), lg superfamily (lgSF) proteins, growth factor receptors, membrane-bound growth factors, and novel proteins. By targeting tetraspanins, which lie at the center of these complexes, a large number of new cell surface interactions can be uncovered at once.

Three types of projects are ongoing in the lab. First, we are continuing to identify the components of tetraspanin complexes. Currently, we are focusing on TM4SF2, a tetraspanin that is associated with X-linked mental retardation. Identifying TM4SF2 molecular partners has the potential to reveal novel functional relationships between proteins required for normal brain function. Second, we are studying key interaction sites within tetraspanin complexes required for their formation, maintenance, and function. Here we are focusing on a complex organized by tetraspanins CD9, CD81, and CD151. These tetraspanins collaborate to link a3b1 integrin (a receptor for the extracellular matrix protein, laminin-5) to lgSF proteins EWI-2 and EWI-F (FPRP) (see adjacent figure). Third, we are developing methods for perturbing tetraspanin complexes and testing the effects on two important types of cell motility: tumor cell migration and neurite regeneration in neuronal cells. The information we uncover may ultimately contribute to strategies for inhibiting tumor cell metastasis or encouraging the re-growth of damaged nerves. For example, we recently found that silencing tetraspanin CD151 by RNA interference markedly impairs α3β1 integrin-dependent carcinoma cell motility on laminin-5.

Selected Publications

1. Winterwood NE, Varzavand A, Meland MN, Ashman LK, Stipp CS. A critical role for tetraspanin CD151 in alpha3beta1 and alpha6beta4 integrin-dependent tumor cell functions on laminin-5. Mol Biol Cell. 2006 Jun;17(6):2707-21.

2. Little KD, Hemler ME, Stipp CS. Dynamic regulation of a GPCR-tetraspanin-G protein complex on intact cells: central role of CD81 in facilitating GPR56-Galpha q/11 association. Mol Biol Cell. 2004 May;15(5):2375-87.

3. Stipp CS, Kolesnikova TV, Hemler ME. EWI-2 regulates a3b1 integrin-dependent cell functions on laminin-5. J Cell Biol. 2003 Dec 8;163(5):1167-77.

4. Stipp CS, Kolesnikova TV, Hemler ME. Functional domains in tetraspanin proteins. Trends Biochem Sci 2003. 28(2):106-12.

5. Stipp CS, Kolesnikova TV, Hemler ME. EWI-2 is a major CD9 and CD81 partner, and member of a novel Ig protein subfamily. J Biol Chem 2001; 276:40545-54.

6. Stipp CS, Orlicky D, Hemler ME. FPRP: A major, highly stoichiometirc, highly specific CD81 and CD9-associated protein. J Biol Chem 2001;276:4853-62.

7. Stipp CS, Hemler ME. Transmembrane-4-superfamily proteins CD151 and CD81 associate with a3b1 integrin, and selectively contribute to alpha 3 beta 1-dependent neurite outgrowth. J Cell Sci. 2000. 114:1871-1882