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Updated: Aug 7, 2026

In vivo and in vitro Studies of Adaptor-clathrin Interaction
Published on: January 27, 2011
Rab11-FIP2, an adaptor protein connecting cellular components involved in internalization and recycling of epidermal
Donald N Cullis1, Betsey Philip, James D Baleja
1Department of Biochemistry, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.
Abstract:
Rab11-FIP2 is a member of a newly identified family of Rab11-binding proteins that have been implicated in the function of recycling endosomes. Here we show that Rab11-FIP2 may also be involved with the process of receptor-mediated endocytosis. First we demonstrate that Rab11-FIP2 contains an NPF motif that allows it to bind Reps1, a member of a family of EH domain proteins involved in endocytosis. We also show that Rab11-FIP2 associates with the alpha-adaptin subunit of AP-2 complexes, which are known to recruit receptors into clathrin-coated vesicles. Finally, we find that overexpression of Rab11-FIP2 suppresses the internalization of epidermal growth factor receptors, but not transferrin receptors, through binding sites that promote complex formation with Rab11, Reps1, and alpha-adaptin. These findings suggest that Rab11-FIP2 may participate in the coupling of receptor-mediated endocytosis to the subsequent sorting of receptor-containing vesicles in endosomes.
Insights
Rab11-FIP2 protein binds Reps1 and alpha-adaptin, suggesting a role in receptor-mediated endocytosis. Overexpression of Rab11-FIP2 specifically inhibits epidermal growth factor receptor internalization.
Area of Science:
- Cell biology
- Molecular biology
- Endocytosis research
Background:
- Rab11-binding proteins are involved in recycling endosome function.
- Receptor-mediated endocytosis is a key cellular process for internalizing molecules.
- EH domain proteins and AP-2 complexes play roles in endocytosis.
Purpose of the Study:
- To investigate the potential role of Rab11-FIP2 in receptor-mediated endocytosis.
- To identify binding partners of Rab11-FIP2 involved in endocytic pathways.
- To determine the effect of Rab11-FIP2 on the internalization of specific receptors.
Main Methods:
- Analysis of Rab11-FIP2's NPF motif for Reps1 binding.
- Assessment of Rab11-FIP2 association with the alpha-adaptin subunit of AP-2 complexes.
- Overexpression studies to observe the impact on epidermal growth factor receptor and transferrin receptor internalization.
Main Results:
- Rab11-FIP2 possesses an NPF motif enabling binding to Reps1, an EH domain protein.
- Rab11-FIP2 interacts with alpha-adaptin, a component of AP-2 complexes crucial for receptor recruitment.
- Overexpression of Rab11-FIP2 selectively inhibits epidermal growth factor receptor internalization, not transferrin receptor uptake.
Conclusions:
- Rab11-FIP2 may link receptor-mediated endocytosis to endosomal sorting via interactions with Rab11, Reps1, and alpha-adaptin.
- The findings suggest Rab11-FIP2's specific involvement in the endocytosis pathway of certain receptors, like the epidermal growth factor receptor.
- Rab11-FIP2's function extends beyond recycling endosomes to potentially regulate initial endocytic events.
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