MICAL-L1 is a tubular endosomal membrane hub that connects Rab35 and Arf6 with Rab8a

Traffic. 2012 Jan;13(1):82-93. doi: 10.1111/j.1600-0854.2011.01294.x. Epub 2011 Oct 24.


Endocytosis is a conserved process across species in which cell surface receptors and lipids are internalized from the plasma membrane. Once internalized, receptors can either be degraded or be recycled back to the plasma membrane. A variety of small GTP-binding proteins regulate receptor recycling. Despite our familiarity with many of the key regulatory proteins involved in this process, our understanding of the mode by which these proteins co-operate and the sequential manner in which they function remains limited. In this study, we identify two GTP-binding proteins as interaction partners of the endocytic regulatory protein molecule interacting with casl-like protein 1 (MICAL)-L1. First, we demonstrate that Rab35 is a MICAL-L1-binding partner in vivo. Over-expression of active Rab35 impairs the recruitment of MICAL-L1 to tubular recycling endosomes, whereas Rab35 depletion promotes enhanced MICAL-L1 localization to these structures. Moreover, we demonstrate that Arf6 forms a complex with MICAL-L1 and plays a role in its recruitment to tubular endosomes. Overall, our data suggest a model in which Rab35 is a critical upstream regulator of MICAL-L1 and Arf6, while both MICAL-L1 and Arf6 regulate Rab8a function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factors / genetics
  • ADP-Ribosylation Factors / metabolism*
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Cell Culture Techniques
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Endocytosis
  • Endosomes / metabolism*
  • Endosomes / ultrastructure
  • HeLa Cells
  • Humans
  • Immunoprecipitation
  • Intracellular Membranes / metabolism*
  • Intracellular Membranes / ultrastructure
  • LIM Domain Proteins / genetics
  • LIM Domain Proteins / metabolism*
  • Microscopy, Confocal
  • Protein Transport
  • RNA Interference
  • Real-Time Polymerase Chain Reaction
  • Two-Hybrid System Techniques
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins
  • LIM Domain Proteins
  • MICAL1 protein, human
  • RAB35 protein, human
  • RAB8A protein, human
  • ADP-Ribosylation Factors
  • ADP-ribosylation factor 6
  • rab GTP-Binding Proteins