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Cited by 12Cellular transport and secretionProtein Kinase Regulation and GTPase SignalingMetabolism, Diabetes, and Cancer

Ral's engagement with the exocyst: Breaking up is hard to do

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Chen, Xiao-Wei, Saltiel, Alan R.·2011·Cell Cycle
DOI 10.4161/cc.10.14.16524
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Abstract

Small GTPases are key intermediates that operate at the crossroads of signaling and trafficking. During insulin-stimulated glucose transport, activation of the vesicular-localized small GTPase RalA leads to its engagement with the vesicle tethering exocyst complex, mediating the plasma membrane targeting of Glut4 vesicles. Activation of RalA is achieved via inhibition of the Ral GAP Complex (RGC), comprised of the regulatory subunit RGC1 and the catalytic subunit RGC2. RGC1/2 share homology with the Rheb GAP complex TSC1/2 and can also be inactivated by Akt-catalyzed phosphorylation to produce RalA activation and exocyst engagement. Disengagement between the GTPase and the exocyst occurs through phosphorylation of its effector Sec5 in its Ral-binding domain, thus allowing continuation of exocytic program and recycling of the tether. Phosphorylation of Sec5 is catalyzed by protein kinase C (PKC) and can be reversed by an exocyst-associated phosphatase activity. Therefore, integration of the GTPase cycle and the phosphorylation cycle orchestrates the engagement-disengagement switch between Ral GTPases and the effector exocyst.

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  • Ral can control exocytotic functions when localized to recycling endosomes, as in its interaction with the exocyst complex to regulate GLUT4 trafficking in adipocytes and myocytes.

    “Ral can control exocytotic functions when localized to recycling endosomes, as is the case when it interacts with the exocyst complex to regulate GLUT4 trafficking in adipocytes and myocytes 37”

    From Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover (2026) · cites this paper as [37]

    In “Ral’s engagement with the exocyst” (page not provided), the paper says RalA resides on GLUT4-containing vesicles and interacts with the exocyst to target those vesicles to the plasma membrane; it also discusses GLUT4 exocytosis in adipocytes and myocytes. It does not identify recycling endosomes as RalA’s location in that GLUT4-trafficking mechanism. Its reference to RalA-dependent recycling-endosome trafficking concerns cytokinesis. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Ral proteins regulate a number of cellular functions and are best characterized for their interaction with the exocyst complex in mediating the targeting and tethering of exocytotic vesicles.

    “Ral proteins regulate a number of cellular functions and are best characterized for their interaction with the exocyst complex in mediating the targeting and tethering of exocytotic vesicles 37 .”

    From Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover (2026) · cites this paper as [37]

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Cited by

Sorted by citations

Authors
Chen, X.-W., & Saltiel, A. R.
Corresponding author
Saltiel, Alan R.
ORCID
Saltiel, Alan R.
Venue
Cell Cycle
Publisher
Informa UK Limited
Published
2011-07-15
Volume
10
Issue
14
Pages
2299-2304
ISSN
  • 1538-4101 (ISSN-L)
  • 1551-4005
DOI
10.4161/cc.10.14.16524
OpenAlex
W2160507929
Cited by
12
References
0
Citations by year
2026: 1 · 2025: 1 · 2021: 1 · 2017: 1 · 2015: 2 · 2013: 3 · 2012: 3
FWCI
0.92
Type
journal article
Language
en
Open access
Locations
  • Cell Cycle (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords
RalA, exocyst complex, small GTPases, protein kinase C, Akt phosphorylation, insulin-stimulated glucose transport, vesicle tethering, GTPase cycle
MeSH terms
Tuberous Sclerosis Complex 1 Protein, Tuberous Sclerosis Complex 2 Protein, Exocytosis, Humans, Phosphorylation, Protein Kinase C, Protein Structure, Tertiary, GTPase-Activating Proteins, ral GTP-Binding Proteins, Tumor Suppressor Proteins, Vesicular Transport Proteins, Proto-Oncogene Proteins c-akt, Glucose Transporter Type 4

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