Submitted January 24, 2008
Accepted March 16, 2008
Integrin 
E(CD103)
7 influences cellular shape and motility in a ligand-dependent fashion
Stephanie Schlickum, Helga Sennefelder, Mike Friedrich, Gregory Harms, Martin J. Lohse, Peter Kilshaw, and Michael P. Schon*
Rudolf-Virchow-Center, DFG Research Center for Experimental Biomedicine, University of Wurzburg, Wurzburg, Germany
Institute of Pharmacology and Toxicology, University of Wurzburg, Wurzburg, Germany
The Babraham Institute, Cambridge, United Kingdom
Department of Dermatology and Venereology, University Medical Center Gottingen, Gottingen, Germany
* Corresponding author; email: michael.schoen{at}med.uni-goettingen.de.
While the extravasation cascade of lymphocytes is well characterized, data on their intraepithelial positioning and morphology are scant. However, the latter process is presumably crucial for many immune functions. Integrin 
E(CD103)
7 has previously been implicated in epithelial retention of some T-cells through binding to E-cadherin. Our current data suggest that E(CD103)7 also determines shape and motility of some lymphocytes. Time-lapse microscopy showed that wildtype E(CD103)7 conferred the ability to form cell protrusions/filopodia and to move in an amoeboid fashion on E-cadherin, an activity that was abrogated by E(CD103)7-directed antibodies or cytochalasin D. The E-dependent motility was further increased (P=0.0003) when point-mutated E(CD103) locked in a constitutively active conformation was expressed. Moreover, different YFP-coupled E(CD103) species demonstrated that the number and length of filopodia extended towards purified E-cadherin, co-cultured keratinocytes, cryostat-cut skin sections or epidermal sheets depended on functional E(CD103). The in vivo relevance of these findings was demonstrated by wildtype dendritic epidermal T-cells (DETC), which showed significantly more dendrites and spanned larger epidermal areas as compared to DETC of E(CD103)-deficient mice (P<0.001). Thus, integrin E(CD103)7 is not only involved in epithelial retention, but also in shaping and proper intraepithelial morphogenesis of some leukocytes.
