PgmNr D1264: The functional impact of Synaptojanin phosphorylation by the Minibrain kinase during synaptic vesicle recycling in Drosophila.

Authors:
Karen Chang; Liping Wang; Junhua Geng; Jooyeun Lee


Institutes
University of Southern California, Los Angeles, CA.


Keyword: other ( synaptic vesicle recycling )

Abstract:

Impaired synaptic transmission is a pathological alteration commonly found in various neurological disorders.  The rapid recycling of synaptic vesicles during stimulation is essential for the sustained function of the nervous system, and clathrin-mediated endocytosis is one prominent molecular pathway in synaptic vesicle recycling. Synaptojanin (Synj), a phosphoinositide phosphatase, plays an important role in endocytosis and is responsible for the uncoating of clathrin during the process.  Previously, we identified that minibrain (Mnb), homolog of the mammalian dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), is a serine/threonine kinase required for normal synaptic growth and rapid synaptic vesicle endocytosis at the Drosophila neuromuscular junction.  We also found that Synj is a substrate of Mnb.  However, site on Synj phosphorylated by Mnb has not been identified and functional consequences underlying Mnb-dependent phosphorylation of Synj are also not well understood.  Here, we show that Mnb phosphorylates Synj at Serine1029 in vivo.   Phosphorylation of Synj at S1029 is required to maintain normal synaptic vesicle recycling in vivo, but is not required to sustain neurotransmission during high frequency stimulation.  It is interesting to note that both Mnb and Synj are upregulated in Down syndrome (DS) and Synj is mutated in Parkinson’s disease.  An understanding of mechanisms that modulate Synj function will thus provide valuable insights into basic mechanisms affecting neuronal communication and lead to strategies to treat these neurological disorders.



Flybase Genetic Index:
1. FlyBase gene symbol: synj; FBgn: 0034691
2. FlyBase gene symbol: mnb; FBgn: 0259168