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The Role of Gap Junctions in Cell Migration

DeFranco, Bado Hewa (2009) The Role of Gap Junctions in Cell Migration. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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The Role of Gap Junctions in Cellular Migration Bado Hewa DeFranco, MS.University of Pittsburgh, 2009The body of work presented here focuses on characterizing the role that gap junction intercellular channels play in regulating cellular migration. Cell migration is a ubiquitous process that is required for embryonic development and for maintaining the integrity of tissues and organs. Yet, the status of gap junction channels, with regard to structure and function, in migrating cells is not completely understood. We hypothesized that, "Gap junction channels, as mediators of intercellular communication, play a role in cell migration," and have investigated and characterized gap junctions in migrating cells. Accordingly, the aims of this dissertation were: (i) to characterize gap junctions and their function during migration, (ii) to determine the effect of altering the status of gap junction expression on cell migration and to (iii) characterize the mechanism of gap junction internalization in migrating cells. With combined molecular and imaging approaches we have demonstrated that in cells migrating as a sheet, gap junction plaque structures are retained on the plasma membrane surface; that gap junction communication is continuous in migrating cells and that interrupting this communication with connexin 43 specific mimetic peptides reduces migration. We have established a system in a human adrenal cortical cell line (SW13) wherein we significantly reduce gap junction protein expression with siRNA and show that cellular migration is inhibited. We have also demonstrated that gap junction plaque size and orientation are modified during migration. We also discovered that sometimes, migrating cells will spontaneously detach from one another at cellular processes and that during this event the gap junction plaques are internalized. Analysis of gap junction plaque internalization in migrating cells revealed that clathrin and several adaptor proteins associate with surface gap junctions and cytoplasmic annular gap junction structures and possibly regulate the unique mechanism of gap junction plaque removal from the plasma membrane. Within the field of gap junction research this work expands our understanding of gap junctions in living cells as dynamic structures that may play a key role in coordinating the migration of entire cell populations.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
DeFranco, Bado
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairDrain, Peterdrain@pitt.eduDRAIN
Committee MemberZhao, Allanazhao@pitt.eduAZHAO
Committee MemberLagenaur, Carllagenaur@pitt.eduLAGENAUR
Committee MemberHackam,
Committee MemberSundarRaj, Nirmalasundarrajn@upmc.eduNIRMALA
Committee MemberMurray, Sandrasmurray@pitt.eduSMURRAY
Date: 27 October 2009
Date Type: Completion
Defense Date: 3 September 2009
Approval Date: 27 October 2009
Submission Date: 12 October 2009
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Cell Biology and Molecular Physiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: ; cell migration; connexins; gap junctions
Other ID:, etd-10122009-153156
Date Deposited: 10 Nov 2011 20:02
Last Modified: 19 Dec 2016 14:37


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