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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 : Journal of molecular biology

Heparan sulfate saccharides modify focal adhesions: implication in mucopolysaccharidosis neuropathophysiology

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Journal of molecular biology - 28 Sep 2014

Bruyère J, Roy E, Ausseil J, Lemonnier T, Teyre G, Bohl D, Etienne-Manneville S, Lortat-Jacob H, Heard JM, Vitry S

Link to Pubmed [PMID] – 25268803

J. Mol. Biol. 2015 Feb;427(4):775-91

Mucopolysaccharidoses type III (MPSIII, Sanfilippo syndrome) are genetic diseases due to deficient heparan sulfate (HS) saccharide digestion by lysosomal exoglycanases. Progressive accumulation of undigested saccharides causes early-onset behavioural and cognitive symptoms. The precise role of these saccharides in the pathophysiological cascade is still unclear. We showed that exposure of wild-type neural cells to exogenous soluble HS fragments of at least eight saccharides activated integrin-based focal adhesions (FAs), which attach cells to the extracellular matrix. FAs were constitutively activated in MPSIII type B astrocytes or neural stem cells unless undigested saccharides were cleared by exogenous supply of the missing exoglycanase. Defective cell polarisation and oriented migration in response to focal extracellular stimuli in affected cells suggest improper sensing of the environment. We consistently observed abnormal organisation of the rostral migratory stream in the brain of adult mice with MPSIII type B. These results suggest that cell polarisation and oriented migration defects participate to the neurological disorders associated with Sanfilippo syndrome.

http://www.ncbi.nlm.nih.gov/pubmed/25268803