Drosophila PAT1 is required for Kinesin-1 to transport cargo and to maximize its motility

Abstract

SUMMARYKinesin heavy chain (KHC), the force-generating component of Kinesin-1, is required for the localization of oskar mRNA and the anchoring of the nucleus in the Drosophila oocyte. These events are crucial for the establishment of the anterior-posterior and dorsal-ventral axes. KHC is also essential for the localization of Dynein and for all ooplasmic flows. Interestingly, oocytes without Kinesin light chain show no major defects in these KHC-dependent processes, suggesting that KHC binds its cargoes and is activated by a novel mechanism. Here, we shed new light on the molecular mechanism of Kinesin function in the germline. Using a combination of genetic, biochemical and motor-tracking studies, we show that PAT1, an APP-binding protein, interacts with Kinesin-1, functions in the transport of oskar mRNA and Dynein and is required for the efficient motility of KHC along microtubules. This work suggests that the role of PAT1 in cargo transport in the cell is linked to PAT1 function as a positive regulator of Kinesin motility.

A Genetic Screen Based onin VivoRNA Imaging Reveals Centrosome-Independent Mechanisms for LocalizinggurkenTranscripts inDrosophila

“…Evidence for the linkage of kinesin and dynein activities comes from studies showing that mid-stage Khc mutant oocytes have reduced Dhc levels (Loiseau et al 2010) and that klc embryos are sensitive to reduced dynein activity (Duncan and Warrior 2002). Dynein activity is also altered in piRNA pathway mutants (Navarro et al 2009), in which centromeric clustering is also impaired (Figure 7, F and H).…”

TRIM3 Regulates the Motility of the Kinesin Motor Protein KIF21B

“…Sunday driver binding to the kinesin heavy chain (KHC) tail is suggested to relieve the inhibition of the tail domain, thereby activating or opening KHC to bind microtubules for long-range motility [41]. Other factors that positively regulate kinesin motility include Drosophila Pat1 that transports oskar mRNA in Drosophila oocytes [42] and the Ran binding protein 2 (RanBP2), which activates the ATPase activity of KHC, thereby potentially regulating kinesin velocity and processivity [43]. Neuronal proteins that regulate the transport direction include huntingtin (htt).…”

Molecular motors: directing traffic during RNA localization

“…Thus, kinesin could localize oskar RNA indirectly; kinesin-1 is required for cytoplasmic flows which could mediate the accumulation of oskar mRNA at the posterior pole (Palacios and St Johnston, 2002), or oskar mRNA could be linked to an organelle localized by kinesin-1. However, recent results indicate that oskar mRNA may be linked to kinesin-1 by a novel KLC-like protein(Loiseau et al, 2010), potentially explaining the independence of oskar RNA transport from canonical kinesin light chain.…”