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Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
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Properly folded and assembled proteins are selectively packaged into vesicles that exit the ER. Motor proteins transport these vesicles to the Golgi apparatus for adding modifications that make these proteins functional at their destination.
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ARF GTPases Function at the Golgi.

Petia Adarska1, Luis Wong-Dilworth1, Francesca Bottanelli2

  • 1Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany.

Sub-Cellular Biochemistry
|February 20, 2026
PubMed
Summary
This summary is machine-generated.

ADP-ribosylation factors (ARFs) are small GTPases regulating intracellular transport. Their GDP-GTP cycle, controlled by GEFs and GAPs, is vital for membrane trafficking and cargo selection.

Keywords:
ARF GTPasesGDP-GTP exchange factorsGTPase activating proteinsGolgi trafficking

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • ADP-ribosylation factors (ARFs) are small GTPases essential for intracellular transport in eukaryotic cells.
  • ARFs regulate membrane trafficking by cycling between GDP-bound inactive and GTP-bound active states.
  • Their function is intrinsically linked to lipid signaling pathways and the recruitment of coat proteins.

Purpose of the Study:

  • To elucidate the regulatory mechanisms of ARF GTPases in intracellular transport.
  • To highlight the role of the GDP-GTP cycle in ARF activation and membrane association.
  • To emphasize the interplay between ARFs, lipid signaling, and coat protein complexes in cargo selection.

Main Methods:

  • The study focuses on the functional cycle of ARFs, involving guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs).
  • It examines the molecular interactions governing ARF membrane recruitment and dissociation.
  • The research integrates knowledge of ARF structure, function, and regulation within the context of cellular trafficking pathways.

Main Results:

  • ARF activation occurs through GEF-mediated GDP-to-GTP exchange, promoting membrane association.
  • ARF inactivation is mediated by GAP-stimulated GTP hydrolysis, leading to membrane dissociation.
  • This dynamic cycle is critical for recruiting specific cargo adaptors and coat proteins, thereby directing vesicle formation and cargo sorting.

Conclusions:

  • The GDP-GTP cycling of ARFs is a fundamental mechanism controlling intracellular membrane trafficking.
  • ARFs act as key molecular switches, integrating signals from lipid modifications and protein interactions.
  • Understanding ARF regulation provides insights into the complex processes of cargo selection and the maintenance of cellular organization.