New findings on polarized membrane trafficking for axon development

Time:2014-02-11

  Neurons are highly polarized cells with a single long axon sending out information and multiple and arborized dendrites receiving information. Usually, the length and area of the single axon are much larger than that of total dendrites, and thus it is believed that there is asymmetric delivery of membrane to these two subcellular compartments. It has been postulated that the post-Golgi pleiomorphic plasmalemmal precursor vesicles (PPVs) act as the source for lipids and membrane proteins required for the polarized membrane supply.

  Recently, the research group headed by Dr. LUO Zhenge has shown that Rab10, a member of Rab family of small GTPases, is associated with PPVs (Wang et al., Dev. Cell 2011), and that Myosin V interaction with Rab10 controls sorting of PPVs from the trans-Golgi network (Liu et al., Nat. Commun. 2013). However, how the Rab10-positive PPVs are delivered to their destinations is totally unknown. Here they show that c-Jun-amino-terminal kinase-interacting protein 1 (JIP1) interacts with GTP-locked active form of Rab10 and directly connects Rab10 to kinesin-1 light chain (KLC). The kinesin-1/JIP1/Rab10 complex is required for anterograde transport of PPVs during axonal growth. Down-regulation of JIP1 or KLC or disrupting the formation of this complex reduces anterograde transport of PPVs in developing axons and causes neuronal polarity defect. Furthermore, this complex plays an important role in neocortical neuronal polarization of rats in vivo. Thus, this study has demonstrated a mechanism underlying directional membrane trafficking involved in axon development.

  This research entitled “JIP1 mediates anterograde transport of Rab10 cargos during neuronal polarization” was published in the Journal of Neuroscience on Jan. 29th, 2014. This work was mainly done by graduate student DENG Caiyun under the supervision of Dr. LUO. This study was supported by grants from National Natural Science Foundation and the Ministry of Science and Technology of China. 

  

  Proposed model for anterograde transport of Rab10-PPVs along the axon. Rab10-PPVs are loaded to kinesin-1 (KIF5) by JIP1, which binds to KLC directly, and transported along microtubules during axon development.

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