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© Emeline Camand
Marquage par immunofluorescence d'astrocytes tumoraux ou astrocytomes (lignée cellulaire humaine U373), montrant en rouge, APC et en vert, la tubuline des microtubules. APC est un supresseur de tumeur qui est impliqué dans la polarisation des astrocytes normaux. La localisation d'APC est altérée dans des lignées de gliomes. Pour essayer de corriger, les dérèglements observés lors de la migration des cellules d'astrocytes tumuraux ou gliomes on cherche à connaitre les mécanismes moléculaires fondamentaux qui controlent la polarisation et la migration cellulaire.
Publication : eLife

Spectrin binding motifs regulate Scribble cortical dynamics and polarity function

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in eLife - 09 Feb 2015

Boëda B, Etienne-Manneville S

Link to Pubmed [PMID] – 25664942

Elife 2015;4

The tumor suppressor protein Scribble (SCRIB) plays an evolutionary conserved role in cell polarity. Despite being central for its function, the molecular basis of SCRIB recruitment and stabilization at the cell cortex is poorly understood. Here we show that SCRIB binds directly to the CH1 domain of β spectrins, a molecular scaffold that contributes to the cortical actin cytoskeleton and connects it to the plasma membrane. We have identified a short evolutionary conserved peptide motif named SADH motif (SCRIB ABLIMs DMTN Homology) which is necessary and sufficient to mediate protein interaction with β spectrins. The SADH domains contribute to SCRIB dynamics at the cell cortex and SCRIB polarity function. Furthermore, mutations in SCRIB SADH domains associated with spina bifida and cancer impact the stability of SCRIB at the plasma membrane, suggesting that SADH domain alterations may participate in human pathology.