uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
The atypical Rho GTPases Miro-1 and Miro-2 have essential roles in mitochondrial trafficking
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
2006 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 344, no 2, 500-510 p.Article in journal (Refereed) Published
Abstract [en]

We recently described the atypical Rho GTPases Miro-1 and Miro-2. These proteins have tandem GTP-binding domains separated by a linker region with putative calcium-binding motives. In addition, the Miro GTPases have a C-terminal transmembrane domain, which confers targeting to the mitochondria. It was reported previously that a constitutively active mutant of Miro-1 induced a clustering of the mitochondria. This response can be separated into two distinct phenotypes: a formation of aggregated mitochondria and the appearance of thread-like mitochondria probably caused by defects in mitochondrial trafficking. The first GTPase domain is required for the clustering of the mitochondria, but the effect is not dependent on the EF-hands. Miro-2 only induces aggregation and not the formation of thread-like mitochondria. Moreover, we show that Miro interacts with the Kinesin-binding proteins, GRIF-1 and OIP106, suggesting that the Miro GTPases form a link between the mitochondria and the trafficking apparatus of the microtubules.

Place, publisher, year, edition, pages
2006. Vol. 344, no 2, 500-510 p.
Keyword [en]
Animals, COS Cells, Cell Line, Cercopithecus aethiops, Humans, Kidney/*metabolism, Mitochondria/*metabolism, Mitochondrial Proteins/genetics/*metabolism, Protein Transport/physiology, Research Support; Non-U.S. Gov't, Structure-Activity Relationship, rho GTP-Binding Proteins/genetics/*metabolism
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-96849DOI: 10.1016/j.bbrc.2006.03.163PubMedID: 16630562OAI: oai:DiVA.org:uu-96849DiVA: diva2:171564
Available from: 2008-03-20 Created: 2008-03-20 Last updated: 2013-10-30Bibliographically approved
In thesis
1. Cell signaling by Rho and Miro GTPases: Studies of Rho GTPases in Cytoskeletal Reorganizations and of Miro GTPases in Mitochondrial Dynamics
Open this publication in new window or tab >>Cell signaling by Rho and Miro GTPases: Studies of Rho GTPases in Cytoskeletal Reorganizations and of Miro GTPases in Mitochondrial Dynamics
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The Ras superfamily of GTPases embraces six major branches of proteins: the Ras, Rab, Ran, Arf, Rho and Miro subfamilies. The majority of GTPases function as binary switches that cycle between active GTP-bound and inactive GDP-bound states. This thesis will focus primarily on the biological functions of the Rho and Miro proteins. The Rho GTPases control the organization of the actin cytoskeleton and other associated activities, whereas the Miro GTPases are regulators of mitochondrial movement and morphology.

A diverse array of cellular phenomena, including cell movement and intracellular membrane trafficking events, are dependent on cytoskeletal rearrangements mediated by Rho GTPases. Although human Rho GTPases are encoded by 20 distinct genes, most studies involving Rho GTPases have focused on the three representatives RhoA, Rac1 and Cdc42, which each regulate specific actin-dependent cellular processes. In an effort to compare the effects of all Rho GTPase members in the same cell system, we transfected constitutively active Rho GTPases in porcine aortic endothelial (PAE) cells and examined their effects on the organization of the actin cytoskeleton. We identified a number of previously undetected roles of the different members of the Rho GTPases. Moreover, we demonstrated that the downstream effectors of Rho GTPases have a broader specificity than previously thought.

In a screen for novel Ras-like GTPases, we identified the Miro GTPases (Mitochondrial Rho). In our characterization of Miro, we established that these proteins influence mitochondrial morphology and serve functions in the transport of mitochondria along the microtubule system. Additionally, we provided evidence that Miro can be under control of calcium signaling pathways. Mitochondria are highly dynamic organelles that undergo continuous change in shape and distribution. Defects in mitochondrial dynamics are associated with several neurodegenerative diseases. In conclusion, our findings have contributed to a deeper understanding of the biological roles of Rho and Miro GTPases.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 74 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 320
Keyword
Ras superfamily, Rho GTPases, cytoskeleton, Miro GTPases, mitochondrial dynamics
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-8514 (URN)978-91-554-7122-4 (ISBN)
Public defence
2008-04-10, B42, Uppsala Biomedical Center, BMC, Husarg. 3, Uppsala, 09:15
Opponent
Supervisors
Available from: 2008-03-20 Created: 2008-03-20Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
Ludwig Institute for Cancer Research
In the same journal
Biochemical and Biophysical Research Communications - BBRC
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 733 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf