title: Spectrin binding motifs regulate Scribble cortical dynamics and polarity function.
abstract: 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.
authors: Cell Polarity, Migration and Cancer Unit, Institut Pasteur - CNRS UMR 3691, Paris, France.
authors: Batiste
authors: B
authors: Boëda
authors: Cell Polarity, Migration and Cancer Unit, Institut Pasteur - CNRS UMR 3691, Paris, France.
authors: Sandrine
authors: S
authors: Etienne-Manneville
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D002460:Cell Line; D016764:Cell Polarity / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D013049:Spectrin / Q000737:chemistry / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*
chemical_list: D008565:Membrane Proteins; C480591:SCRIB protein, human; D025521:Tumor Suppressor Proteins; D013049:Spectrin
keywords: biochemistry; cancer; cell biology; cortical cytoskeleton; human; mouse; polarity; protein–protein interaction; spina bifida