Protein 4.1R binds to CLASP2 and regulates dynamics, organization and attachment of microtubules to the cell cortex.
The microtubule (MT) cytoskeleton is essential for many cellular processes, including cell polarity and migration. Cortical platforms, formed by a subset of MT plus-end-tracking proteins, such as CLASP2, and non-MT binding proteins such as LL5β, attach distal ends of MTs to the cell cortex. However, the mechanisms involved in organizing these platforms have not yet been described in detail. Here we show that 4.1R, a FERM-domain-containing protein, interacts and colocalizes with cortical CLASP2 and is required for the correct number and dynamics of CLASP2 cortical platforms. Protein 4.1R also controls binding of CLASP2 to MTs at the cell edge by locally altering GSK3 activity. Furthermore, in 4.1R-knockdown cells MT plus-ends were maintained for longer in the vicinity of cell edges, but instead of being tethered to the cell cortex, MTs continued to grow, bending at cell margins and losing their radial distribution. Our results suggest a previously unidentified role for the scaffolding protein 4.1R in locally controlling CLASP2 behavior, CLASP2 cortical platform turnover and GSK3 activity, enabling correct MT organization and dynamics essential for cell polarity.
Centro de Biología Molecular Severo Ochoa and Departamento de Biología Molecular, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid (CSIC and UAM), Nicolás Cabrera 1, 28049 Madrid, Spain.
Ana
A
Ruiz-Saenz
Jeffrey
J
van Haren
C Laura
CL
Sayas
Laura
L
Rangel
Jeroen
J
Demmers
Jaime
J
Millán
Miguel A
MA
Alonso
Niels
N
Galjart
Isabel
I
Correas
D002465:Cell Movement / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary
C497851:CLASP2 protein, human; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C028841:erythrocyte membrane band 4.1 protein
CLASP2; Cortical platforms; Microtubule dynamics; Microtubule organization; Protein 4.1R