Abstract
BackgroundMany membrane proteins, including Drosophila Dscam, are enriched in dendrites or axons within neurons. However, little is known about how the differential distribution is established and maintained.Methodology/Principal FindingsHere we investigated the mechanisms underlying the dendritic targeting of Dscam[TM1]. Through forward genetic mosaic screens and by silencing specific genes via targeted RNAi, we found that several genes, encoding various components of the dynein-dynactin complex, are required for restricting Dscam[TM1] to the mushroom body dendrites. In contrast, compromising dynein/dynactin function did not affect dendritic targeting of two other dendritic markers, Nod and Rdl. Tracing newly synthesized Dscam[TM1] further revealed that compromising dynein/dynactin function did not affect the initial dendritic targeting of Dscam[TM1], but disrupted the maintenance of its restriction to dendrites.Conclusions/SignificanceThe results of this study suggest multiple mechanisms of dendritic protein targeting. Notably, dynein-dynactin plays a role in excluding dendritic Dscam, but not Rdl, from axons by retrograde transport.
Highlights
Neurons exhibit highly polarized structures, including two morphologically and functionally distinct domains, axons and dendrites
We have previously shown that transgenic Down Syndrome cell adhesion molecule (Dscam) carrying the exon 17.1-encoding transmembrane domain is selectively targeted to dendrites
We reasoned that incorporating Dscam[TM1]::GFP into our MARCM screens should allow us to uncover genes, regardless of their possible involvement in other essential cellular events, that are essential for proper dendritic targeting of Dscam[TM1]::GFP
Summary
Neurons exhibit highly polarized structures, including two morphologically and functionally distinct domains, axons and dendrites. In the mammalian brain and in cultured neurons, voltage-gated potassium channels of the Kv1 (Shaker) family reside in the axons. Voltage-gated potassium channel Kv2.1 and Kv2.2 are selectively enriched in the somatodendritic region [1,2,3]. The dendritic potassium channels undergo slower inactivation to prevent back-propagation of action potentials into the dendrites [4,5]. Certain metabotropic glutamate receptors, including mGluR1a and mGluR2, show polarized distribution [6], and potentially underlie differential glutamate effects in different compartments of neurons [7,8]. Many membrane proteins, including Drosophila Dscam, are enriched in dendrites or axons within neurons. Little is known about how the differential distribution is established and maintained
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