Mechanistic insights into regulated cargo binding by ACAP1 protein
Ming Bai1, Xiaoyun Pang, Jizhong Lou
1Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, and the Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
The Journal of Biological Chemistry
|May 31, 2012
Summary
This study reveals how Akt phosphorylation regulates integrin recycling by ACAP1 (ArfGAP with coiled-coil, ankyrin repeat, and PH domains protein 1). It uncovers a mechanism where phosphorylation relieves autoinhibition, enhancing cargo binding for controlled protein transport.
Area of Science:
- Cellular biology
- Molecular mechanisms of protein transport
- Endocytic recycling pathways
Background:
- Coat complexes mediate protein sorting into vesicular transport pathways.
- GTPase-activating proteins (GAPs) for ADP-ribosylation factor (ARF) GTPases are key regulators.
- ACAP1 (ArfGAP with coiled-coil, ankyrin repeat, and PH domains protein 1) is an ARF6 GAP involved in endocytic recycling.
Purpose of the Study:
- To elucidate the mechanistic insights into how Akt phosphorylation regulates cargo binding by ACAP1.
- To understand the role of ACAP1 in integrin recycling.
- To define the regulatory juncture controlling integrin recycling.
Main Methods:
- Structural studies
- Computational modeling
- Functional assays
- Identification of a critical integrin β1 cytoplasmic domain sequence
Main Results:
- A critical sequence in integrin β1 acts as a recycling sorting signal recognized by ACAP1.
- Phosphorylation of ACAP1 by Akt relieves localized autoinhibition.
- This relief enhances ACAP1's cargo binding, thereby regulating integrin recycling.
Conclusions:
- ACAP1's cargo binding is regulated by phosphorylation-mediated relief of autoinhibition.
- This mechanism provides key regulatory control over integrin recycling.
- The study advances the understanding of how regulated cargo binding drives regulated transport.
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