Reference Report

Reference
Citation	Lee, S., Liu, H.P., Lin, W.Y., Guo, H., Lu, B. (2010). LRRK2 kinase regulates synaptic morphology through distinct substrates at the presynaptic and postsynaptic compartments of the Drosophila neuromuscular junction. J. Neurosci. 30(50): 16959--16969. (Export to RIS)
FlyBase ID	FBrf0212570
Publication Type	Research paper
PubMed ID	21159966
PubMed Abstract	Mutations in leucine-rich repeat kinase 2 (LRRK2) are linked to familial as well as sporadic forms of Parkinson's disease (PD), a neurodegenerative disease characterized by dysfunction and degeneration of dopaminergic and other types of neurons. The molecular and cellular mechanisms underlying LRRK2 action remain poorly defined. Here, we show that LRRK2 controls synaptic morphogenesis at the Drosophila neuromuscular junction. Loss of Drosophila LRRK2 results in synaptic overgrowth, whereas overexpression of Drosophila LRRK or human LRRK2 has opposite effects. Alteration of LRRK2 activity also affects neurotransmission. LRRK2 exerts its effects on synaptic morphology by interacting with distinct downstream effectors at the presynaptic and postsynaptic compartments. At the postsynapse, LRRK2 interacts with the previously characterized substrate 4E-BP, an inhibitor of protein synthesis. At the presynapse, LRRK2 phosphorylates and negatively regulates the microtubule (MT)-binding protein Futsch. These results implicate synaptic dysfunction caused by deregulated protein synthesis and aberrant MT dynamics in LRRK2 pathogenesis and offer a new paradigm for understanding and ultimately treating PD.
DOI	10.1523/JNEUROSCI.1807-10.2010
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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^Lrrk
Alleles (18)
	Avic\GFP^{S65T.Scer\UAS.T:Ivir\HA1,T:Hsap\mito} futsch^EP1419 futsch^K68 futsch^N94 Hsap\LRRK2^{G2019S.Scer\UAS.T:Zzzz\FLAG} Hsap\LRRK2^{Scer\UAS.T:Zzzz\FLAG} kay^Fbz.Scer\UAS Lrrk^3KD.Scer\UAS Lrrk^e03680 Lrrk^{I1915T.Scer\UAS} Lrrk^Scer\UAS.cIa par-1^Scer\UAS.cSa Scer\GAL4^da.G32 Scer\GAL4^elav-C155 Scer\GAL4^Mhc.PW Thor^k13517 Thor^Scer\UAS.cMa Thor^TA.Scer\UAS
Constructs (12)
	P{GAL4-da.G32} P{GAL4-Mhc.W} P{UAS-Fra.Fbz} P{UAS-LRRK2.FLAG} P{UAS-LRRK2.G2019S.FLAG} P{UAS-Lrrk.3KD} P{UAS-Lrrk.I1915T} P{UAS-Lrrk.I} P{UAS-mito-HA-GFP.AP} P{UAS-par-1.S} P{UAS-Thor.TA} P{UAS-Thor.wt}
Genes (10)
	Avic\GFP Csp dlg1 futsch Hsap\LRRK2 kay Lrrk par-1 Scer\GAL4 Thor
Insertions (4)
	P{EP}futsch^EP1419 P{GawB}elav^C155 P{lacW}Thor^k13517 PBac{RB}Lrrk^e03680
Natural transposons (1)
	P-element