dc.contributor.author
Barth, Carolin
dc.date.accessioned
2020-02-06T09:50:30Z
dc.date.available
2020-02-06T09:50:30Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/26593
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-26350
dc.description.abstract
Rho family GTPases are key regulators of cytoskeletal dynamics and control all aspects of cellular morphogenesis, ranging from migration to adhesion. They function as molecular switches that cycle between an inactive GDP-bound state and an active GTP-bound state, in which they can engage with numerous downstream effectors. Rho signalling requires tight spatiotemporal control which is mediated by in total 145 Rho guanine nucleotide exchange factors (RhoGEFs) and Rho GTPase activating proteins (RhoGAPs) in humans. These proteins encode a broad spectrum of targeting and protein interaction domains and thereby contribute specificity to Rho signalling.
During development, wound healing or metastasis, cells must change their positions within organs or the entire body. This is achieved by guided cell migration, where attractive or repulsive signals in the extracellular environment direct cells towards distinct positions. A well-studied class of guidance molecules is the SLIT ligand family that upon binding to their ROBO recep- tors directs repulsive migration in diverse tissues. The underlying processes are orchestrated by Rho GTPases, however, the downstream RhoGEFs and RhoGAPs that link the receptors to the GTPases are only poorly characterized and also have not been fully identified. Moreover, for the structurally distinct endothelial-specific ROBO4 receptor so far no regulator has been found at all.
In Drosophila melanogaster the RhoGAP Vilse/Crossgap, which is the homologue of the novel human RhoGAP ARHGAP39, has been linked to Robo signalling, as its depletion causes misrouting of tracheal ganglionic branches and axons in the central nervous system (CNS). Furthermore in a previous mass spectrometry screen for RhoGEF/GAP interactors (Müller et al., BioRxiv) ROBO4 was identified as binding partner for ARHGAP39. Motivated by the possible interaction of mammalian ARHGAP39 with all human ROBO receptors, I aimed to functionally characterize ARHGAP39 and to investigate its function in guided cell migration.
Together, my studies yielded insights into the role of ARHGAP39 in cell motility, both in randomly migrating cells and in SLIT2/ROBO-dependent guided migration, and provide the framework for future mechanistic studies.
en
dc.format.extent
XII, 185 Seiten
dc.rights.uri
http://www.fu-berlin.de/sites/refubium/rechtliches/Nutzungsbedingungen
dc.subject
RhoGTPase signaling
en
dc.subject
cell migration
en
dc.subject
angiogenesis
en
dc.subject
GTPase activating protein (GAP)
en
dc.subject
SLIT/ROBO guidance system
en
dc.subject.ddc
500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie::570 Biowissenschaften; Biologie
dc.title
The Role of ARHGAP39 in cell migration
dc.contributor.gender
female
dc.contributor.firstReferee
Sigrist, Stephan
dc.contributor.furtherReferee
Rocks, Oliver
dc.date.accepted
2019-02-22
dc.identifier.urn
urn:nbn:de:kobv:188-refubium-26593-4
dc.title.translated
Die Rolle von ARHGAP39 während der Zellmigration
de
refubium.affiliation
Biologie, Chemie, Pharmazie
dcterms.accessRights.dnb
free
dcterms.accessRights.openaire
open access
dcterms.accessRights.proquest
accept