Elimination of redundant synapses formed early in development and strengthening of necessary connections are crucial for shaping functional neural circuits. Purkinje cells (PCs) in the neonatal cerebellum are innervated by multiple climbing fibers (CFs) with similar strengths. A single CF is strengthened whereas the other CFs are eliminated in each PC during postnatal development. The underlying mechanisms, particularly for the strengthening of single CFs, are poorly understood. Here we report that progranulin, a multi-functional growth factor implicated in the pathogenesis of frontotemporal dementia, strengthens developing CF synaptic inputs and counteracts their elimination from postnatal day 11 to 16. Progranulin derived from PCs acts retrogradely onto its putative receptor Sort1 on CFs. This effect is independent of semaphorin 3A, another retrograde signaling molecule that counteracts CF synapse elimination. We propose that progranulin-Sort1 signaling strengthens and maintains developing CF inputs, and may contribute to selection of single "winner" CFs that survive synapse elimination.
Pubmed ID: 29398357 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This polyclonal targets mouse parvalbumin (NM013645)
View all literature mentionsThis polyclonal targets mouse GLAST, C-terminal 41 aa (NM148938)
View all literature mentionsThis polyclonal targets mouse VGAT, 31-112 aa(BC052020)
View all literature mentionsThis polyclonal targets VGluT2
View all literature mentionsThis polyclonal targets VGluT2, 520-582 aa (BC038375)
View all literature mentionsThis polyclonal targets mouse Car8, 33-61 aa (BC010773)
View all literature mentions