Reference Report

Reference
Citation	Weng, Y.L., Liu, N., Diantonio, A., Broihier, H.T. (2011). The Cytoplasmic Adaptor Protein Caskin Mediates Lar Signal Transduction during Drosophila Motor Axon Guidance. J. Neurosci. 31(12): 4421--4433. (Export to RIS)
FlyBase ID	FBrf0213321
Publication Type	Research paper
PubMed ID	21430143
PubMed Abstract	The multiprotein complexes that receive and transmit axon pathfinding cues during development are essential to circuit generation. Here, we identify and characterize the Drosophila sterile α-motif (SAM) domain-containing protein Caskin, which shares homology with vertebrate Caskin, a CASK [calcium/calmodulin-(CaM)-activated serine-threonine kinase]-interacting protein. Drosophila caskin (ckn) is necessary for embryonic motor axon pathfinding and interacts genetically and physically with the leukocyte common antigen-related (Lar) receptor protein tyrosine phosphatase. In vivo and in vitro analyses of a panel of ckn loss-of-function alleles indicate that the N-terminal SAM domain of Ckn mediates its interaction with Lar. Like Caskin, Liprin-α is a neuronal adaptor protein that interacts with Lar via a SAM domain-mediated interaction. We present evidence that Lar does not bind Caskin and Liprin-α concurrently, suggesting they may assemble functionally distinct signaling complexes on Lar. Furthermore, a vertebrate Caskin homolog interacts with LAR family members, arguing that the role of ckn in Lar signal transduction is evolutionarily conserved. Last, we characterize several ckn mutants that retain Lar binding yet display guidance defects, implying the existence of additional Ckn binding partners. Indeed, we identify the SH2/SH3 adaptor protein Dock as a second Caskin-binding protein and find that Caskin binds Lar and Dock through distinct domains. Furthermore, whereas ckn has a nonredundant function in Lar-dependent signaling during motor axon targeting, ckn and dock have overlapping roles in axon outgrowth in the CNS. Together, these studies identify caskin as a neuronal adaptor protein required for axon growth and guidance.
DOI	10.1523/JNEUROSCI.5230-10.2011
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Language of Publication	English
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Publication Type	Journal
Abbreviation	J. Neurosci.
Title	Journal of Neuroscience
Publication Year	1981-
ISBN/ISSN	0270-6474 1529-2401
Data from Reference
Aberrations (1)
	Df(2R)BSC330
Alleles (22)
	ckn^{A.R305Q.Scer\UAS} ckn^A.R305Q ckn^{C.Δ750-806.Scer\UAS} ckn^C.Δ750-806 ckn^D.Q593stop ckn^F.Q402stop ckn^{K.Δ324-331.Scer\UAS} ckn^K.Δ324-331 ckn^L.Q34stop ckn^Scer\UAS.cWa ckn^X.Q403stop ckn^{Y.A909V.Scer\UAS} ckn^Y.A909V dock³ dock⁰⁴⁷²³ Lar^5.5 Lar^13.2 Mmus\caskin2^SAM.Scer\UAS Ptp69D¹ Ptp69D⁷ Scer\GAL4^elav.PLu Scer\GAL4^exex-Gal4
Constructs (8)
	P{GAL4-elav.L} P{GSV1} P{UAS-ckn.A909V} P{UAS-ckn.R305Q} P{UAS-ckn.W} P{UAS-ckn.Δ324-331} P{UAS-ckn.Δ750-806} P{UAS-mCaskin2.SAM}
Genes (9)
	CG4393 ckn dock Fas2 Lar Liprin-α Mmus\caskin2 Ptp69D Scer\GAL4
Insertions (2)
	P{GawB}exex^Gal4 P{GSV1}GS1205
Natural transposons (1)
	P-element