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Intrinsic tethering activity of endosomal Rab proteins.

Rab small G proteins control membrane trafficking events required for many processes including secretion, lipid metabolism, antigen presentation and growth factor signaling. Rabs recruit effectors that mediate diverse functions including vesicle tethering and fusion. However, many mechanistic questions about Rab-regulated vesicle tethering are unresolved. Using chemically defined reaction systems, we discovered that Vps21, a Saccharomyces cerevisiae ortholog of mammalian endosomal Rab5, functions in trans with itself and with at least two other endosomal Rabs to directly mediate GTP-dependent tethering. Vps21-mediated tethering was stringently and reversibly regulated by an upstream activator, Vps9, and an inhibitor, Gyp1, which were sufficient to drive dynamic cycles of tethering and detethering. These experiments reveal a previously undescribed mode of tethering by endocytic Rabs. In our working model, the intrinsic tethering capacity Vps21 operates in concert with conventional effectors and SNAREs to drive efficient docking and fusion.

Pubmed ID: 22157956


  • Lo SY
  • Brett CL
  • Plemel RL
  • Vignali M
  • Fields S
  • Gonen T
  • Merz AJ


Nature structural & molecular biology

Publication Data

January 5, 2012

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM077349
  • Agency: NCRR NIH HHS, Id: P41 RR11823
  • Agency: NIGMS NIH HHS, Id: R01 GM077349
  • Agency: NIGMS NIH HHS, Id: R01 GM077349-05
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Endocytosis
  • Endosomes
  • GTP-Binding Proteins
  • GTPase-Activating Proteins
  • Guanine Nucleotide Exchange Factors
  • Guanosine Diphosphate
  • Guanosine Triphosphate
  • Liposomes
  • Microscopy, Electron, Transmission
  • Mutation
  • Protein Binding
  • SNARE Proteins
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Two-Hybrid System Techniques
  • Vesicular Transport Proteins
  • rab GTP-Binding Proteins