AI Article Synopsis
- The study investigates how AGAP1, a GTPase-activating protein, regulates the cytoskeleton, which is crucial for cell movement.
- AGAP1 interacts with the motor protein Kif2A through its GLD and PH domains, enhancing Kif2A's activity and influencing cell migration and spreading.
- Knockdown experiments reveal that both AGAP1 and Kif2A play important roles in maintaining proper cell dynamics, and their activity is linked to a functional protein complex necessary for cytoskeleton remodeling.
Article Abstract
The molecular basis for control of the cytoskeleton by the Arf GTPase-activating protein AGAP1 has not been characterized. AGAP1 is composed of G-protein-like (GLD), pleckstrin homology (PH), Arf GAP, and ankyrin repeat domains. Kif2A was identified in screens for proteins that bind to AGAP1. The GLD and PH domains of AGAP1 bound the motor domain of Kif2A. Kif2A increased GAP activity of AGAP1, and a protein composed of the GLD and PH domains of AGAP1 increased ATPase activity of Kif2A. Knockdown (KD) of Kif2A or AGAP1 slowed cell migration and accelerated cell spreading. The effect of Kif2A KD on spreading could be rescued by expression of Kif2A-GFP or FLAG-AGAP1, but not by Kif2C-GFP. The effect of AGAP1 KD could be rescued by FLAG-AGAP1, but not by an AGAP1 mutant that did not bind Kif2A efficiently, ArfGAP1-HA or Kif2A-GFP. Taken together, the results support the hypothesis that the Kif2A·AGAP1 complex contributes to control of cytoskeleton remodeling involved in cell movement.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5076806 | PMC |
| http://dx.doi.org/10.1074/jbc.M116.732479 | DOI Listing |
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