Rab33a and Rab33ba mediate the outgrowth of forebrain commissural axons in the zebrafish brain

Liguo Huang,Akihiro Urasaki,Naoyuki Inagaki

doi:10.1038/s41598-018-38468-5

Liguo Huang, Akihiro Urasaki + Show 1 more

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https://doi.org/10.1038/s41598-018-38468-5

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Journal: Scientific Reports	Publication Date: Feb 12, 2019
Citations: 8	License type: open-access

Affiliation: Nara Institute of Science and Technology

Abstract

Rab small GTPases play key roles in intracellular membrane trafficking. Rab33a promotes axon outgrowth of cultured rat hippocampal neurons by mediating the anterograde axonal transport of Golgi-derived vesicles and the concomitant exocytosis of these vesicles at the growth cone. However, the functions of Rab33 in vivo are unclear. Here, we show that zebrafish rab33a and rab33ba are orthologs of mammalian Rab33a and Rab33b, respectively. They are expressed in the developing brain, including in neurons of the telencephalic dorsorostral cluster and the diencephalic ventrorostral cluster, which project axons to form the anterior and postoptic commissures, respectively. Although rab33a single mutant and rab33ba single mutant fish did not show remarkable defects, fish carrying the rab33a;rab33ba double mutations displayed dysgenesis of the anterior and postoptic commissures. Single-cell labeling in the telencephalic dorsorostral cluster demonstrated that the rab33a;rab33ba double mutation inhibits axonal extension in the anterior commissure. These results suggest that Rab33a and Rab33ba mediate axon outgrowth and the formation of the forebrain commissures in the zebrafish brain in a cooperative manner.

Highlights

Axon outgrowth requires rapid expansion of the plasma membrane[1]
With regard to the mechanism for axonal membrane expansion, our previous study with cultured hippocampal neurons demonstrated that Rab33a promotes anterograde axonal transport of the post-Golgi vesicles, which is associated with vesicular exocytosis at the growth cones and axon outgrowth[14]
We show that zebrafish rab33a and rab33ba are orthologs of mammalian Rab33a and Rab33b, respectively, and that rab33a and rab33ba mediate the outgrowth of forebrain commissural axons in the developing zebrafish brain

Summary

Introduction

Axon outgrowth requires rapid expansion of the plasma membrane[1]. Axonal membrane expansion is mediated by multiple processes, including membrane synthesis at the rough endoplasmic reticulum and Golgi apparatus in the cell body, vesicular transport along the axonal shaft, and vesicular exocytosis at the growth cone[1,2,3,4,5]. Rab family proteins are key regulators of intracellular vesicular trafficking pathways[6,7,8,9,10]. They localize to specific membrane compartments and function as molecular switches that cycle between the GTP-bound active form and the GDP-bound inactive form[6,7,8,9,10]. With regard to the mechanism for axonal membrane expansion, our previous study with cultured hippocampal neurons demonstrated that Rab33a promotes anterograde axonal transport of the post-Golgi vesicles, which is associated with vesicular exocytosis at the growth cones and axon outgrowth[14]. We show that zebrafish rab33a and rab33ba are orthologs of mammalian Rab33a and Rab33b, respectively, and that rab33a and rab33ba mediate the outgrowth of forebrain commissural axons in the developing zebrafish brain

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Conclusion