Kinesin Heavy Chain Function inDrosophilaGlial Cells Controls Neuronal Activity

Abstract

Kinesin heavy chain (Khc) is crucially required for axonal transport and khc mutants show axonal swellings and paralysis. Here, we demonstrate that in Drosophila khc is equally important in glial cells. Glial-specific downregulation of khc by RNA interference suppresses neuronal excitability and results in spastic flies. The specificity of the phenotype was verified by interspecies rescue experiments and further mutant analyses. Khc is mostly required in the subperineurial glia forming the blood-brain barrier. Following glial-specific knockdown, peripheral nerves are swollen with maldistributed mitochondria. To better understand khc function, we determined Khcdependent Rab proteins in glia and present evidence that Neurexin IV, a well known blood-brain barrier constituent, is one of the relevant cargo proteins. Our work shows that the role of Khc for neuronal excitability must be considered in the light of its necessity for directed transport in glia.

The effects of ER morphology on synaptic structure and function in Drosophila melanogaster

“…Transmitter release at the Drosophila neuromuscular junction can be affected by the target muscle or the neighboring peripheral glia (Huang and Stern, 2002;Kerr et al, 2014;McCabe et al, 2003;Schmidt et al, 2012). RNAi-mediated atl knockdown in muscle or glia did not affect transmitter release or frequency of synaptic failures (Fig.…”

“…This finding is consistent with previous data demonstrating that proper synaptic transmission requires intercellular signaling among these three cell types. In particular, loss of activity within the peripheral glia of the kinesin heavy chain gene or the inebriated-encoded neurotransmitter transporter alters evoked transmitter release (Huang and Stern, 2002;Schmidt et al, 2012). In addition, the peripheral glia secrete at least two proteins, the TGF-β ligand Maverick and Wingless/Wnt, that regulate synaptic function (Fuentes-Medel et al, 2012;Kerr et al, 2014).…”

Glial Glycolysis Is Essential for Neuronal Survival in Drosophila

“…To address glial glycolysis in adult flies, we employed the Gal80 ts -based TARGET system (McGuire et al, 2003). The island assay was performed as described (Schmidt et al, 2012). The 20-kb-large deficiency Df(2R)DTret was generated by FRT-Flp-mediated recombination using P{RS5} elements 5-HA-1641 and 5-HA-2258 (Ryder et al, 2004;Thibault et al, 2004).…”

A transcriptional network controlling glial development in theDrosophilavisual system

“…About 60 genes were missed by our FlyBase query compared with the list by Hens et al (2011). To obtain strong gene silencing we employed a strain with two copies of repo-Gal4 (Schmidt et al, 2012). We did not include dicer2, as this resulted in unspecific phenotypes.…”