No abstract

Rab35 mediates membrane trafficking between the plasma membrane and the early endosomes at the cell surface. Our understanding of the cellular function of Rab35 reveals its role in development and diseases. In the developmental context, Rab35 has been shown to play an important role in regulating epithelial polarity, lumen opening, myoblast fusion, intercalation of epithelium, myelination, neurite outgrowth, and oocyte meiotic maturation. Disruption of recycling endosome mediated by Rab35 has been linked to several neurological diseases, including Parkinson's disease and Down syndrome. In addition, because Rab35 modulates cell migration through its interaction with various effectors, Rab35 plays an important role in cancers. Lastly, the Rab35-mediated recycling endosomal pathway and exocytosis is utilized by pathogens or hijacked by pathogens to promote their infection and survival. This review summarizes the function of Rab35 in endocytosis and focuses on the role of Rab35 in the context of development and diseases.

Fascin is a conserved protein that has been shown to modulate the cytoskeleton. Its role in early development remains unclear. After fertilization, embryos undergo rapid cell divisions, requiring the precise regulation of cytoskeleton to segregate chromosomes. Results indicate that Fascin is in the cell cortex, enriched in the perinuclear region of non-dividing blastomeres and on the mitotic spindle of dividing blastomeres of the early embryo. Loss-of-function of Fascin leads to a significant developmental delay or arrest, indicating that Fascin is important for proper early embryonic development.

miR-31 is a highly conserved microRNA that plays critical roles in cell proliferation, migration, and differentiation. We discovered miR-31 and some of its validated targets are enriched on the mitotic spindle of the dividing sea urchin embryo and mammalian cells. Using the sea urchin embryo, we found that miR-31 inhibition led to developmental delay correlated with increased cytoskeleton and chromosomal defects. We identified miR-31 to directly suppress several actin remodeling transcripts, β-actin, Gelsolin, Rab35 and Fascin, which were localized to the mitotic spindle. miR-31 inhibition leads to increased newly translated Fascin at the spindles. Forced ectopic localization of Fascin transcripts to the cell membrane and translation led to significant developmental and chromosomal segregation defects, leading to our hypothesis that miR-31 regulates local translation at the mitotic spindle to ensure proper cell division. Furthermore, miR-31-mediated post-transcriptional regulation at the mitotic spindle may be an evolutionarily conserved regulatory paradigm of mitosis.