Homologs of eukaryotic Ras superfamily proteins in prokaryotes and their novel phylogenetic correlation with their eukaryotic analogs

Dong, Jiuhong; Wen, Jianfan; Tian, Huanfang

doi:10.1016/j.gene.2007.03.001

Cited by 49 publications

(43 citation statements)

References 31 publications

(41 reference statements)

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“…Along with SAR1, the ARFs and ARLs comprise the ARF family [16]. These proteins were present in the earliest eukaryotes and have been predicted to have arisen in prokaryotes [17]. ARFs have been shown to regulate membrane traffic both directly through recruitment of protein adaptors (the focus of this review) and perhaps less directly via regulation of lipid modifying enzymes that contribute to membrane deformation or signaling.…”

Section: Specificity Of Arf Activation By Gefsmentioning

confidence: 99%

Regulating the large Sec7 ARF guanine nucleotide exchange factors: the when, where and how of activation

Wright

Kahn

Sztul

2014

Cell. Mol. Life Sci.

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Eukaryotic cells require selective sorting and transport of cargo between intracellular compartments. This is accomplished at least in part by vesicles that bud from a donor compartment, sequestering a subset of resident protein “cargos” destined for transport to an acceptor compartment. A key step in vesicle formation and targeting is the recruitment of specific proteins that form a coat on the outside of the vesicle in a process requiring the activation of regulatory GTPases of the ARF family. Like all such GTPases, ARFs cycle between inactive, GDP-bound, and membrane-associated active, GTP-bound, conformations. And like most regulatory GTPases the activating step is slow and thought to be rate limiting in cells, requiring the use of ARF guanine nucleotide exchange factor (GEFs). ARF GEFs are characterized by the presence of a conserved, catalytic Sec7 domain, though they also contain motifs or additional domains that confer specificity to localization and regulation of activity. These domains have been used to define and classify five different sub-families of ARF GEFs. One of these, the BIG/GBF1 family, includes three proteins that are each key regulators of the secretory pathway. GEF activity initiates the coating of nascent vesicles via the localized generation of activated ARFs and thus these GEFs are the upstream regulators that define the site and timing of vesicle production. Paradoxically, while we have detailed molecular knowledge of how GEFs activate ARFs, we know very little about how GEFs are recruited and/or activated at the right time and place to initiate transport. This review summarizes the current knowledge of GEF regulation and explores the still uncertain mechanisms that position GEFs at “budding ready” membrane sites to generate highly localized activated ARFs.

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Section: Specificity Of Arf Activation By Gefsmentioning

confidence: 99%

Regulating the large Sec7 ARF guanine nucleotide exchange factors: the when, where and how of activation

Wright

Kahn

Sztul

2014

Cell. Mol. Life Sci.

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“…Thus, while ARL2 clearly localizes to mitochondria, its function(s) there are poorly understood. The ARF and RAS families of GTPases are predicted to have arisen in prokaryotes [17] and thus specific roles in mitochondrial biology may be among the most ancient signaling pathways known to have survived the emergence of eukaryotes. Therefore, a role for a nuclear encoded regulatory GTPase inside mitochondria is expected to provide potentially important insights into both mitochondrial and evolutionary biology.…”

Section: Introductionmentioning

confidence: 99%

The ARL2 GTPase Is Required for Mitochondrial Morphology, Motility, and Maintenance of ATP Levels

et al. 2014

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ARF-like 2 (ARL2) is a member of the ARF family and RAS superfamily of regulatory GTPases, predicted to be present in the last eukaryotic common ancestor, and essential in a number of model genetic systems. Though best studied as a regulator of tubulin folding, we previously demonstrated that ARL2 partially localizes to mitochondria. Here, we show that ARL2 is essential to a number of mitochondrial functions, including mitochondrial morphology, motility, and maintenance of ATP levels. We compare phenotypes resulting from ARL2 depletion and expression of dominant negative mutants and use these to demonstrate that the mitochondrial roles of ARL2 are distinct from its roles in tubulin folding. Testing of current models for ARL2 actions at mitochondria failed to support them. Rather, we found that knockdown of the ARL2 GTPase activating protein (GAP) ELMOD2 phenocopies two of three phenotypes of ARL2 siRNA, making it a likely effector for these actions. These results add new layers of complexity to ARL2 signaling, highlighting the need to deconvolve these different cell functions. We hypothesize that ARL2 plays essential roles inside mitochondria along with other cellular functions, at least in part to provide coupling of regulation between these essential cell processes.

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“…Fully folded proteins are transported by importins, which shuttle between cyto-and nucleoplasm (through the pore complexes). The major structural motif of importin-b, the HEAT repeats (Morimoto et al 2002), the Ras-like GTPase RAN, facilitating export of importins (Dong et al 2007) as well as RAN-GDP import factor NTF2 (Mans et al 2004), originated from bacterial ancestors (Bohnsack and Schleiff 2010). COPII-coat proteins and nucleoporins share structural features and arrangements (Devos et al 2004;Sampathkumar et al 2013) and therefore most likely a common ancestry (Brohawn et al 2008;Debler et al 2008;Kampmann and Blobel 2009), arguing for a coevolution of the endomembrane system and the nuclear envelope.…”

Section: The First Days Of Eukaryotic Protein Traffickingmentioning

confidence: 99%

Protein Targeting and Transport as a Necessary Consequence of Increased Cellular Complexity

Sommer

Schleiff

2014

Cold Spring Harbor Perspectives in Biology

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Homologs of eukaryotic Ras superfamily proteins in prokaryotes and their novel phylogenetic correlation with their eukaryotic analogs

Cited by 49 publications

References 31 publications

Regulating the large Sec7 ARF guanine nucleotide exchange factors: the when, where and how of activation

Regulating the large Sec7 ARF guanine nucleotide exchange factors: the when, where and how of activation

The ARL2 GTPase Is Required for Mitochondrial Morphology, Motility, and Maintenance of ATP Levels

Protein Targeting and Transport as a Necessary Consequence of Increased Cellular Complexity

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