Regulation of the hDlg/hScrib/Hugl-1 tumour suppressor complex.
The proper function of the Scribble tumour suppressor complex is dependent upon the correct localisation of its components. Previously we observed dynamic relocalisation of the hDlg component under conditions of osmotic stress. We now show that the other two components of the complex, hScrib and Hugl-1 display similar patterns of expression. We demonstrate, by shRNA ablation of hScrib expression, that hDlg and Hugl-1 are in part dependent upon hScrib for their correct localization. However under conditions of osmotic stress this apparent dependency no longer exists: hDlg and Hugl-1 localise to cell membranes independently of hScrib. We also demonstrate an interaction between the three components of the hScrib complex and the tSNARE syntaxin 4, and show that correct localization of the Scrib complex is in part tSNARE dependent. This is the first detailed analysis of the co-localisation and function of the hScrib complex in mammalian cells and demonstrates a direct link between the control of the hScrib complex and vesicle transport pathways.
Massimi
Paola
P
International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34012 Trieste, Italy. paola@icgeb.org
Narayan
Nisha
N
Thomas
Miranda
M
Gammoh
Noor
N
Strand
Susanne
S
Strand
Dennis
D
Banks
Lawrence
L
D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D000074288:Discs Large Homolog 1 Protein; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism; D009994:Osmolar Concentration; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D050765:Qa-SNARE Proteins / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D013012:Sorbitol / Q000494:pharmacology; D022161:Transport Vesicles / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C513314:DLG1 protein, human; D000074288:Discs Large Homolog 1 Protein; C097906:LLGL1 protein, human; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D050765:Qa-SNARE Proteins; C480591:SCRIB protein, human; D025521:Tumor Suppressor Proteins; D013012:Sorbitol