Title: The neurotrophic properties of progranulin depend on the granulin E domain but do not require sortilin binding
Authors: De Muynck, Louis *
Herdewyn, Sarah *
Beel, Sander
Scheveneels, Wendy
Van Den Bosch, Ludo
Robberecht, Wim
Van Damme, Philip # ×
Issue Date: Nov-2013
Publisher: Elsevier
Series Title: Neurobiology of aging vol:34 issue:11 pages:2541-7
Article number: S0197-4580(13)00187-5
Abstract: Progranulin (PGRN) is a growth factor involved in wound healing, inflammation, tumor growth, and neurodegeneration. Mutations in the gene encoding PGRN give rise to shortage of PGRN and cause familial frontotemporal lobar degeneration. PGRN exerts neurotrophic functions and binding of PGRN to the membrane receptor sortilin (SORT1) mediates the endocytosis of PGRN. SORT1-mediated uptake plays an important role in the regulation of extracellular PGRN levels. We studied the role of SORT1 in PGRN-mediated neuroprotection in vitro and in vivo. The survival-enhancing effect of PGRN seemed to be dependent on the granulin E (GRN E) domain. Pharmacologic inhibition of the GRN E-SORT1 interaction or deletion of the SORT1 binding site of GRN E did not abolish its neurotrophic function. In addition, the in vivo phenotype of PGRN knockdown in zebrafish embryos was not phenocopied by SORT1 knockdown. These results suggest that GRN E mediates the neurotrophic properties of PGRN and that binding to SORT1 is not required for this effect.
ISSN: 0197-4580
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for Neurobiology (Vesalius Research Center)
* (joint) first author
× corresponding author
# (joint) last author

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