Reference Report

Reference
Citation	Medina, P.M., Worthen, R.J., Forsberg, L.J., Brenman, J.E. (2008). The actin-binding protein capulet genetically interacts with the microtubule motor kinesin to maintain neuronal dendrite homeostasis. PLoS ONE 3(8): e3054. (Export to RIS)
FlyBase ID	FBrf0205725
Publication Type	Research paper
PubMed ID	18725959
PubMed Abstract	Neurons require precise cytoskeletal regulation within neurites, containing microtubule tracks for cargo transport in axons and dendrites or within synapses containing organized actin. Due to the unique architecture and specialized function of neurons, neurons are particularly susceptible to perturbation of the cytoskeleton. Numerous actin-binding proteins help maintain proper cytoskeletal regulation.From a Drosophila forward genetic screen, we identified a mutation in capulet--encoding a conserved actin-binding protein--that causes abnormal aggregates of actin within dendrites. Through interaction studies, we demonstrate that simultaneous genetic inactivation of capulet and kinesin heavy chain, a microtubule motor protein, produces elongate cofilin-actin rods within dendrites but not axons. These rods resemble actin-rich structures induced in both mammalian neurodegenerative and Drosophila Alzheimer's models, but have not previously been identified by loss of function mutations in vivo. We further demonstrate that mitochondria, which are transported by Kinesin, have impaired distribution along dendrites in a capulet mutant. While Capulet and Cofilin may biochemically cooperate in certain circumstances, in neuronal dendrites they genetically antagonize each other.The present study is the first molecularly defined loss of function demonstration of actin-cofilin rods in vivo. This study suggests that simultaneous, seemingly minor perturbations in neuronal dendrites can synergize producing severe abnormalities affecting actin, microtubules and mitochondria/energy availability in dendrites. Additionally, as >90% of Alzheimer's and Parkinson's cases are sporadic this study suggests mechanisms by which multiple mutations together may contribute to neurodegeneration instead of reliance on single mutations to produce disease.
DOI	10.1371/journal.pone.0003054
Related Publication(s)
Recent Updates
Description	What does this section display? This section contains items that were added to this record for each release. It currently only tracks new links between this FlyBase report and other FlyBase data classes (e.g. genes, references, stocks) or controlled vocabulary terms (e.g. GO, anatomy terms). What does this section not display? This section does not currently display links that were removed or gene model changes.
Update Feed	Click the icon below to subscribe to this FlyBase record and receive updates automatically through your feed reader.
FB2013_03
FB2013_02
All updates	Click here to see a list of all updates to this record from FB2010_08 and on.
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
Language of Publication	English
Additional Languages of Abstract
Also Published As
Parent Publication
Publication Type	Journal
Abbreviation	PLoS ONE
Title	PLoS ONE
Publication Year	2006-
ISBN/ISSN	1932-6203
Data from Reference
Aberrations (3)
	Df(2L)ast5 Df(2L)Exel6004 Df(2L)Exel7006
Alleles (17)
	Act5C^{Scer\UAS.T:Avic\GFP} Avic\GFP^{S65T.Scer\UAS.T:Ivir\HA1,T:Hsap\mito} capt⁰⁶⁹⁵⁵ capt^E636 capt^K304 capt^k01217 capt^Scer\UAS.cBa capt^{Scer\UAS.T:Disc\RFP-mCherry} capt^unspecified Disc\RFP^{Scer\UAS.T:Myr-Src64B} Khc^{248-2134.Scer\UAS.T:Avic\GFP-EGFP} Khc^e02141 Khc^k13314 Scer\GAL4^109(2)80 T:Disc\RFP^mCherry tsr^Scer\UAS.cNa w^+mC
Constructs (7)
	P{UAS-Act5C.T:GFP} P{UAS-capt.B} P{UAS-Khc.EGFP} P{UAS-mCherry-capt} P{UAS-mito-HA-GFP.AP} P{UAS-myr-mRFP} P{UAS-tsr.N}
Genes (8)
	Act5C Avic\GFP capt Disc\RFP Khc Scer\GAL4 tsr w
Insertions (1)
	P{GawB}109(2)80
Natural transposons (1)
	P-element