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Progranulin

Definition:

Secreted protein that acts as a key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation. Regulates protein trafficking to lysosomes and, also the activity of lysosomal enzymes. Facilitates also the acidification of lysosomes, causing degradation of mature CTSD by CTSB. In addition, functions as wound-related growth factor that acts directly on dermal fibroblasts and endothelial cells to promote division, migration and the formation of capillary-like tubule structures (By similarity). Also promotes epithelial cell proliferation by blocking TNF-mediated neutrophil activation preventing release of oxidants and proteases. Moreover, modulates inflammation in neurons by preserving neurons survival, axonal outgrowth and neuronal integrity.; [Granulin-4]: Promotes proliferation of the epithelial cell line A431 in culture.; [Granulin-3]: Inhibits epithelial cell proliferation and induces epithelial cells to secrete IL-8.; [Granulin-7]: Stabilizes CTSD through interaction with CTSD leading to maintain its aspartic-type peptidase activity.

References:

[1]. Sander Beel, et al. Progranulin functions as a cathepsin D chaperone to stimulate axonal outgrowth in vivo. Hum Mol Genet. 2017 Aug 1;26(15):2850-2863. [Content Brief]

[2]. Jing Zhu, et al. Conversion of proepithelin to epithelins: roles of SLPI and elastase in host defense and wound repair. Cell. 2002 Dec 13;111(6):867-78. [Content Brief]

[3]. Yoshinori Tanaka, et al. Progranulin regulates lysosomal function and biogenesis through acidification of lysosomes. Hum Mol Genet. 2017 Mar 1;26(5):969-988. [Content Brief]

[4]. Xiaolai Zhou, et al. Impaired prosaposin lysosomal trafficking in frontotemporal lobar degeneration due to progranulin mutations. Nat Commun. 2017 May 25;8:15277. [Content Brief]

[5]. Philip Van Damme, et al. Progranulin functions as a neurotrophic factor to regulate neurite outgrowth and enhance neuronal survival. J Cell Biol. 2008 Apr 7;181(1):37-41. [Content Brief]

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