Yes / The contribution of the actin cytoskeleton to the unique architecture of the Golgi complex is manifold.
An important player in this process is Coronin7 (CRN7), a Golgi-resident protein that stabilizes F-actin
assembly at the trans-Golgi network (TGN) thereby facilitating anterograde trafficking. Here, we
establish that CRN7-mediated association of F-actin with the Golgi apparatus is distinctly modulated
via the small Rho GTPase Cdc42 and N-WASP. We identify N-WASP as a novel interaction partner of
CRN7 and demonstrate that CRN7 restricts spurious F-actin reorganizations by repressing N-WASP
‘hyperactivity’ upon constitutive Cdc42 activation. Loss of CRN7 leads to increased cellular F-actin
content and causes a concomitant disruption of the Golgi structure. CRN7 harbours a Cdc42- and
Rac-interactive binding (CRIB) motif in its tandem β-propellers and binds selectively to GDP-bound
Cdc42N17 mutant. We speculate that CRN7 can act as a cofactor for active Cdc42 generation. Mutation
of CRIB motif residues that abrogate Cdc42 binding to CRN7 also fail to rescue the cellular defects in
fibroblasts derived from CRN7 KO mice. Cdc42N17 overexpression partially rescued the KO phenotypes
whereas N-WASP overexpression failed to do so. We conclude that CRN7 spatiotemporally influences
F-actin organization and Golgi integrity in a Cdc42- and N-WASP-dependent manner. / This work was supported by SFB 670 and DFG NO 113/22. K.B. was supported by a fellowship from the NRW International Graduate School “From Embryo to Old Age: the Cell Biology and Genetics of Health and Disease” (IGSDHD), Cologne.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/17712 |
| Date | 28 February 2020 |
| Creators | Bhattacharya, K., Swaminathan, Karthic, Peche, V.S., Clemen, C.S., Knyphausen, P., Lammers, M., Noegel, A.A., Rastetter, R.H. |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, Published version |
| Rights | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/, CC-BY |
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