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Interaction with the effector dynamin-related protein 1 (Drp1) is an ancient function of Rab32 subfamily proteins.

Ortiz-Sandoval CG, Hughes SC, Dacks JB, Simmen T - Cell Logist (2014)

Bottom Line: The mitochondria-associated membrane (MAM) is an endoplasmic reticulum (ER) domain that forms contacts with mitochondria and accommodates Ca(2+) transfer between the two organelles.Our results now shed light on this conundrum and identify a role in Drp1-mediated mitochondrial dynamics as one common denominator of this group of Rabs, which includes the paralogues Rab32A and Rab32B, as well as the more recently derived Rab29 and Rab38 proteins.Moreover, we provide evidence that this mitochondrial function is dictated by the extent of ER-association of Rab32 family proteins.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Medicine and Dentistry; Department of Cell Biology; University of Alberta ; Edmonton, Alberta, Canada.

ABSTRACT

The mitochondria-associated membrane (MAM) is an endoplasmic reticulum (ER) domain that forms contacts with mitochondria and accommodates Ca(2+) transfer between the two organelles. The GTPase Rab32 regulates this function of the MAM via determining the localization of the Ca(2+) regulatory transmembrane protein calnexin to the MAM. Another function of the MAM is the regulation of mitochondrial dynamics mediated by GTPases such as dynamin-related protein 1 (Drp1). Consistent with the importance of the MAM for mitochondrial dynamics and the role of Rab32 in MAM enrichment, the inactivation of Rab32 leads to mitochondrial collapse around the nucleus. However, Rab32 and related Rabs also perform intracellular functions at locations other than the MAM including melanosomal trafficking, autophagosome formation and maturation, and retrograde trafficking to the trans-Golgi network (TGN). This plethora of functions raises questions concerning the original cellular role of Rab32 in the last common ancestor of animals and its possible role in the last eukaryotic common ancestor (LECA). Our results now shed light on this conundrum and identify a role in Drp1-mediated mitochondrial dynamics as one common denominator of this group of Rabs, which includes the paralogues Rab32A and Rab32B, as well as the more recently derived Rab29 and Rab38 proteins. Moreover, we provide evidence that this mitochondrial function is dictated by the extent of ER-association of Rab32 family proteins.

No MeSH data available.


Related in: MedlinePlus

Distribution of the Rab32 family proteins across eukaryotic taxa. (A). Coulson plot representing the distribution of the Rab32 family proteins across different organisms of the 6 major eukaryotic supergroups. Colored or blank pieces of the pie chart indicate presence or absence of Rabs in each organism, respectively. Numbers indicate when there was more than one homolog found in each specific organism. The non-abbreviated name for each organism is included in their corresponding color boxes. (B). Phylogenetic evolution of Rab32 family proteins. Clades containing sequences of each specific family member are color coded (Rab32A, orange; Rab29, yellow; Rab38, green). Numerical values represent Bayesian posterior probabilities and maximum likelihood bootstrap values (RAxML and PhyML); black circles indicate 1.00/95/95 support values for MrBayes, RAxML, and PhyML, respectively.
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f0001: Distribution of the Rab32 family proteins across eukaryotic taxa. (A). Coulson plot representing the distribution of the Rab32 family proteins across different organisms of the 6 major eukaryotic supergroups. Colored or blank pieces of the pie chart indicate presence or absence of Rabs in each organism, respectively. Numbers indicate when there was more than one homolog found in each specific organism. The non-abbreviated name for each organism is included in their corresponding color boxes. (B). Phylogenetic evolution of Rab32 family proteins. Clades containing sequences of each specific family member are color coded (Rab32A, orange; Rab29, yellow; Rab38, green). Numerical values represent Bayesian posterior probabilities and maximum likelihood bootstrap values (RAxML and PhyML); black circles indicate 1.00/95/95 support values for MrBayes, RAxML, and PhyML, respectively.

Mentions: A grouping of Rab proteins according to their sequence similarity led to the discovery that Rab29, Rab38 and Rab32A/B form a subfamily among the Rabs.26 We first examined when the Rab32 ancestor diversified, via homology searching and phylogenetics. Our study included at least 2 representative organisms from each of the 6 major eukaryotic supergroups, thus improving the taxonomic breadth compared to previous studies.24-26. As shown in Figure 1A, Rab32A and Rab32B are the only members of the family that are present in all supergroups, except Archaeplastida, whereas both Rab38 and Rab29 are Holozoa-specific. Rab32 showed an ancient split very early in evolution, which led to Rab32A and Rab32B (Supplemental Fig. 1), consistent with previous findings.26 Interestingly, we detected that the presence of Rab32B always coincides with the presence of Rab32A, but that Rab32B is lost in Metazoa concurrently with the appearance of Rab38. This raises the possibility that, in this lineage, Rab38 could have taken over redundant functions from Rab32B allowing for loss of the latter. Moreover, Rab29 is never found alone, but always in the presence of at least one of the other family members (Rab32A, Rab38 or Rab32B). Therefore, Rab29 and Rab38 may perform non-redundant functions that have either been added during evolution to the Rab32 repertoire or that have been lost from the ancient Rab32A/B.Figure 1.


Interaction with the effector dynamin-related protein 1 (Drp1) is an ancient function of Rab32 subfamily proteins.

Ortiz-Sandoval CG, Hughes SC, Dacks JB, Simmen T - Cell Logist (2014)

Distribution of the Rab32 family proteins across eukaryotic taxa. (A). Coulson plot representing the distribution of the Rab32 family proteins across different organisms of the 6 major eukaryotic supergroups. Colored or blank pieces of the pie chart indicate presence or absence of Rabs in each organism, respectively. Numbers indicate when there was more than one homolog found in each specific organism. The non-abbreviated name for each organism is included in their corresponding color boxes. (B). Phylogenetic evolution of Rab32 family proteins. Clades containing sequences of each specific family member are color coded (Rab32A, orange; Rab29, yellow; Rab38, green). Numerical values represent Bayesian posterior probabilities and maximum likelihood bootstrap values (RAxML and PhyML); black circles indicate 1.00/95/95 support values for MrBayes, RAxML, and PhyML, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4355727&req=5

f0001: Distribution of the Rab32 family proteins across eukaryotic taxa. (A). Coulson plot representing the distribution of the Rab32 family proteins across different organisms of the 6 major eukaryotic supergroups. Colored or blank pieces of the pie chart indicate presence or absence of Rabs in each organism, respectively. Numbers indicate when there was more than one homolog found in each specific organism. The non-abbreviated name for each organism is included in their corresponding color boxes. (B). Phylogenetic evolution of Rab32 family proteins. Clades containing sequences of each specific family member are color coded (Rab32A, orange; Rab29, yellow; Rab38, green). Numerical values represent Bayesian posterior probabilities and maximum likelihood bootstrap values (RAxML and PhyML); black circles indicate 1.00/95/95 support values for MrBayes, RAxML, and PhyML, respectively.
Mentions: A grouping of Rab proteins according to their sequence similarity led to the discovery that Rab29, Rab38 and Rab32A/B form a subfamily among the Rabs.26 We first examined when the Rab32 ancestor diversified, via homology searching and phylogenetics. Our study included at least 2 representative organisms from each of the 6 major eukaryotic supergroups, thus improving the taxonomic breadth compared to previous studies.24-26. As shown in Figure 1A, Rab32A and Rab32B are the only members of the family that are present in all supergroups, except Archaeplastida, whereas both Rab38 and Rab29 are Holozoa-specific. Rab32 showed an ancient split very early in evolution, which led to Rab32A and Rab32B (Supplemental Fig. 1), consistent with previous findings.26 Interestingly, we detected that the presence of Rab32B always coincides with the presence of Rab32A, but that Rab32B is lost in Metazoa concurrently with the appearance of Rab38. This raises the possibility that, in this lineage, Rab38 could have taken over redundant functions from Rab32B allowing for loss of the latter. Moreover, Rab29 is never found alone, but always in the presence of at least one of the other family members (Rab32A, Rab38 or Rab32B). Therefore, Rab29 and Rab38 may perform non-redundant functions that have either been added during evolution to the Rab32 repertoire or that have been lost from the ancient Rab32A/B.Figure 1.

Bottom Line: The mitochondria-associated membrane (MAM) is an endoplasmic reticulum (ER) domain that forms contacts with mitochondria and accommodates Ca(2+) transfer between the two organelles.Our results now shed light on this conundrum and identify a role in Drp1-mediated mitochondrial dynamics as one common denominator of this group of Rabs, which includes the paralogues Rab32A and Rab32B, as well as the more recently derived Rab29 and Rab38 proteins.Moreover, we provide evidence that this mitochondrial function is dictated by the extent of ER-association of Rab32 family proteins.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Medicine and Dentistry; Department of Cell Biology; University of Alberta ; Edmonton, Alberta, Canada.

ABSTRACT

The mitochondria-associated membrane (MAM) is an endoplasmic reticulum (ER) domain that forms contacts with mitochondria and accommodates Ca(2+) transfer between the two organelles. The GTPase Rab32 regulates this function of the MAM via determining the localization of the Ca(2+) regulatory transmembrane protein calnexin to the MAM. Another function of the MAM is the regulation of mitochondrial dynamics mediated by GTPases such as dynamin-related protein 1 (Drp1). Consistent with the importance of the MAM for mitochondrial dynamics and the role of Rab32 in MAM enrichment, the inactivation of Rab32 leads to mitochondrial collapse around the nucleus. However, Rab32 and related Rabs also perform intracellular functions at locations other than the MAM including melanosomal trafficking, autophagosome formation and maturation, and retrograde trafficking to the trans-Golgi network (TGN). This plethora of functions raises questions concerning the original cellular role of Rab32 in the last common ancestor of animals and its possible role in the last eukaryotic common ancestor (LECA). Our results now shed light on this conundrum and identify a role in Drp1-mediated mitochondrial dynamics as one common denominator of this group of Rabs, which includes the paralogues Rab32A and Rab32B, as well as the more recently derived Rab29 and Rab38 proteins. Moreover, we provide evidence that this mitochondrial function is dictated by the extent of ER-association of Rab32 family proteins.

No MeSH data available.


Related in: MedlinePlus