title: Phospho-regulated Drosophila adducin is a determinant of synaptic plasticity in a complex with Dlg and PIP2 at the larval neuromuscular junction.
abstract: Adducin is a ubiquitously expressed actin- and spectrin-binding protein involved in cytoskeleton organization, and is regulated through phosphorylation of the myristoylated alanine-rich C-terminal kinase (MARCKS)-homology domain by protein kinase C (PKC). We have previously shown that the Drosophila adducin, Hu-li tai shao (Hts), plays a role in larval neuromuscular junction (NMJ) growth. Here, we find that the predominant isoforms of Hts at the NMJ contain the MARCKS-homology domain, which is important for interactions with Discs large (Dlg) and phosphatidylinositol 4,5-bisphosphate (PIP2). Through the use of Proximity Ligation Assay (PLA), we show that the adducin-like Hts isoforms are in complexes with Dlg and PIP2 at the NMJ. We provide evidence that Hts promotes the phosphorylation and delocalization of Dlg at the NMJ through regulation of the transcript distribution of the PAR-1 and CaMKII kinases in the muscle. We also show that Hts interactions with Dlg and PIP2 are impeded through phosphorylation of the MARCKS-homology domain. These results are further evidence that Hts is a signaling-responsive regulator of synaptic plasticity in Drosophila.
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada.
authors.forename: Simon Ji Hau
authors.initials: SJ
authors.lastname: Wang
authors.affiliation: Department of Biomedical Physiology and Kinesiology, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada.
authors.forename: Amy
authors.initials: A
authors.lastname: Tsai
authors.affiliation: Department of Biomedical Physiology and Kinesiology, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada.
authors.forename: Mannan
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada.
authors.forename: SooHyun
authors.initials: S
authors.lastname: Yoo
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada.
authors.forename: Hae-Yoon
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada.
authors.forename: Byoungjoo
authors.initials: B
authors.lastname: Yoo
authors.affiliation: Department of Biomedical Physiology and Kinesiology, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada.
authors.forename: Vincent
authors.initials: V
authors.lastname: Chui
authors.affiliation: Department of Biology, University of Toronto at Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada.
authors.forename: Marta
authors.initials: M
authors.lastname: Kisiel
authors.affiliation: Department of Biology, University of Toronto at Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada.
authors.forename: Bryan
authors.initials: B
authors.lastname: Stewart
authors.affiliation: Department of Biomedical Physiology and Kinesiology, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada.
authors.forename: Wade
authors.initials: W
authors.lastname: Parkhouse
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada nharden@sfu.ca ckrieger@sfu.ca.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Harden
authors.affiliation: Department of Biomedical Physiology and Kinesiology, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada nharden@sfu.ca ckrieger@sfu.ca.
authors.forename: Charles
authors.initials: C
authors.lastname: Krieger
keywords: Adducin; Dlg; Drosophila; Hts; Neuromuscular junction; PIP2