The interaction between progranulin and prosaposin is mediated by granulins and the linker region between saposin B and C
Open accessAbstract
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. image Read the Editorial Comment for this article on page 154.
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Prosaposin heterodimerizes with progranulin, regulating its levels and facilitating its transport to the lysosome.
“Prosaposin heterodimerizes with progranulin, regulating its levels and facilitating its transport to the lysosome35,36.”
From Rare variant associations with plasma protein levels in the UK Biobank (2023) · cites this paper as [35]
The Abstract reports that prosaposin physically interacts with progranulin and helps target it to lysosomes. The Introduction says PSAP polymorphisms affect plasma progranulin levels. The paper describes a complex, but the cited passages do not establish that it is specifically a heterodimer. (LLM, conf=0.83)
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- Authors
- Zhou, X., Sullivan, P. M., Sun, L., & Hu, F.
- Affiliations
- Cornell University (US)
- Corresponding author
- Hu, Fenghua
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2017-08-04
- Volume
- 143
- Issue
- 2
- Pages
- 236-243
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- PMC
- PMC5630500
- OpenAlex
- W2701641415
- Cited by
- 44
- References
- 1
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 5 · 2023: 3 · 2022: 7 · 2021: 4 · 2020: 3 · 2019: 5 · 2018: 2 · 2017: 3
- FWCI
- 1.90
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS088448‐01)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- progranulin, prosaposin, saposin B, saposin C, protein-protein interaction, lysosomal trafficking, frontotemporal lobar degeneration, lysosomal function
- MeSH terms
- Progranulins, Amino Acid Sequence, Animals, Animals, Newborn, Chlorocebus aethiops, Humans, Protein Binding, Protein Precursors, Mice, Knockout, COS Cells, Intercellular Signaling Peptides and Proteins, Saposins, Mice, Rats, HEK293 Cells
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