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- Title
The interaction between progranulin and prosaposin is mediated by granulins and the linker region between saposin B and C.
- Authors
Zhou, Xiaolai; Sullivan, Peter M.; Sun, Lirong; Hu, Fenghua
- Abstract
The frontotemporal lobar degeneration (FTLD) protein progranulin (PGRN) is essential for proper lysosomal function. PGRN localizes in the lysosomal compartment within the cell. Prosaposin (PSAP), the precursor of lysosomal saposin activators (saposin A, B, C, D), physically interacts with PGRN. Previously, we have shown that PGRN and PSAP facilitate each other's lysosomal trafficking. Here, we report that the interaction between PSAP and PGRN requires the linker region of saposin B and C (BC linker). PSAP protein with the BC linker mutated, fails to interact with PGRN and deliver PGRN to lysosomes in the biosynthetic and endocytic pathways. On the other hand, PGRN interacts with PSAP through multiple granulin motifs. Granulin D and E bind to PSAP with similar affinity as full-length PGRN.
- Subjects
FRONTOTEMPORAL lobar degeneration; PROGRANULIN; LYSOSOMAL storage diseases; NEURONAL ceroid-lipofuscinosis; LYSOSOMES
- Publication
Journal of Neurochemistry, 2017, Vol 143, Issue 2, p236
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/jnc.14110