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Background  Many 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 Findings  Here 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/Significance  The 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.

Dynein-Dynactin Complex Is Essential for Dendritic Restriction of TM1-Containing Drosophila Dscam