Cathepsin D and its newly identified transport receptor SEZ6L2 can modulate neurite outgrowth

Marielle Boonen, Catherine Staudt, Florentine Gilis, Viola Oorschot, Judith Klumperman, Michel Jadot

Résultats de recherche: Contribution à un journal/une revueArticleRevue par des pairs


How, in the absence of a functional mannose 6-phosphate (Man-6-P)-signal-dependent transport pathway, some acid hydrolases remain sorted to endolysosomes in the brain is poorly understood. We demonstrate that cathepsin D binds to mouse SEZ6L2, a type 1 transmembrane protein predominantly expressed in the brain. Studies of the subcellular trafficking of SEZ6L2, and its silencing in a mouse neuroblastoma cell line reveal that SEZ6L2 is involved in the trafficking of cathepsin D to endosomes. Moreover, SEZ6L2 can partially correct the cathepsin D hypersecretion resulting from the knockdown of UDP-GlcNAc:lysosomal enzyme GlcNAc-1-phosphotransferase in HeLa cells (i.e. in cells that are unable to synthesize Man-6-P signals). Interestingly, cleavage of SEZ6L2 by cathepsin D generates an N-terminal soluble fragment that induces neurite outgrowth, whereas its membrane counterpart prevents this. Taken together, our findings highlight that SEZ6L2 can serve as receptor to mediate the sorting of cathepsin D to endosomes, and suggest that proteolytic cleavage of SEZ6L2 by cathepsin D modulates neuronal differentiation.

langue originaleAnglais
Pages (de - à)557-68
Nombre de pages12
journalJournal of Cell Science
Numéro de publication3
Les DOIs
Etat de la publicationPublié - 2016

Empreinte digitale

Examiner les sujets de recherche de « Cathepsin D and its newly identified transport receptor SEZ6L2 can modulate neurite outgrowth ». Ensemble, ils forment une empreinte digitale unique.

Contient cette citation