| First Author | Boonen M | Year | 2016 |
| Journal | J Cell Sci | Volume | 129 |
| Issue | 3 | Pages | 557-68 |
| PubMed ID | 26698217 | Mgi Jnum | J:234670 |
| Mgi Id | MGI:5790552 | Doi | 10.1242/jcs.179374 |
| Citation | Boonen M, et al. (2016) Cathepsin D and its newly identified transport receptor SEZ6L2 can modulate neurite outgrowth. J Cell Sci 129(3):557-68 |
| abstractText | 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. |
