Clathrin-mediated endocytosis (CME) involves spatially and temporally restricted molecular dynamics, to which protein kinases and actin contribute. However, whether and how these two elements merge to properly execute CME remains unknown. Here, we show that neural Wiskott-Aldrich syndrome protein (N-WASP) and casein kinase 2 (CK2) form a complex and localize to clathrin-coated vesicles. N-WASP binds to and is phosphorylated by CK2, thereby reducing the kinase activity of CK2. By contrast, N-WASPpromoted actin polymerization is decreased upon both phosphorylation and binding of CK2. Knockdown of CK2 and N-WASP, either alone or in combination, causes a similar inhibition in the initial rate of CME of epidermal growth factor receptor (EGFR) and its accumulation at the plasma membrane. Increased levels of EGFR at the cell surface can only be efficiently rescued by reconstituting the N-WASP-CK2 complex with either wild-type or phosphorylation-mimicking N-WASP and wild-type CK2. Notably, perturbation of N-WASP-CK2 complex function showed that N-WASP controls the presence of F-actin at clathrin-coated structures. In summary, the N-WASP-CK2 complex integrates in a single circuit different activities contributing to CME.

Galovic, M., Xu, D., Areces, L., van der Kammen, R., Innocenti, M. (2011). Interplay between N-WASP and CK2 optimizes clathrin-mediated endocytosis of EGFR. JOURNAL OF CELL SCIENCE, 124(12), 2001-2012 [10.1242/jcs.081182].

Interplay between N-WASP and CK2 optimizes clathrin-mediated endocytosis of EGFR

Innocenti M
2011

Abstract

Clathrin-mediated endocytosis (CME) involves spatially and temporally restricted molecular dynamics, to which protein kinases and actin contribute. However, whether and how these two elements merge to properly execute CME remains unknown. Here, we show that neural Wiskott-Aldrich syndrome protein (N-WASP) and casein kinase 2 (CK2) form a complex and localize to clathrin-coated vesicles. N-WASP binds to and is phosphorylated by CK2, thereby reducing the kinase activity of CK2. By contrast, N-WASPpromoted actin polymerization is decreased upon both phosphorylation and binding of CK2. Knockdown of CK2 and N-WASP, either alone or in combination, causes a similar inhibition in the initial rate of CME of epidermal growth factor receptor (EGFR) and its accumulation at the plasma membrane. Increased levels of EGFR at the cell surface can only be efficiently rescued by reconstituting the N-WASP-CK2 complex with either wild-type or phosphorylation-mimicking N-WASP and wild-type CK2. Notably, perturbation of N-WASP-CK2 complex function showed that N-WASP controls the presence of F-actin at clathrin-coated structures. In summary, the N-WASP-CK2 complex integrates in a single circuit different activities contributing to CME.
Articolo in rivista - Articolo scientifico
Actin cytoskeleton; CK2; Endocytosis; N-WASP
English
2001
2012
12
Galovic, M., Xu, D., Areces, L., van der Kammen, R., Innocenti, M. (2011). Interplay between N-WASP and CK2 optimizes clathrin-mediated endocytosis of EGFR. JOURNAL OF CELL SCIENCE, 124(12), 2001-2012 [10.1242/jcs.081182].
File in questo prodotto:
File Dimensione Formato  
Galovic-2022-J Cell Sci-VoR.pdf

accesso aperto

Descrizione: Research Article
Tipologia di allegato: Publisher’s Version (Version of Record, VoR)
Dimensione 1.59 MB
Formato Adobe PDF
1.59 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/396111
Citazioni
  • Scopus 25
  • ???jsp.display-item.citation.isi??? 24
Social impact