A Caenorhabditis elegans Homologue of LYST Functions in Endosome and Lysosome‐Related Organelle Biogenesis

• Published in: Traffic (Copenhagen, Denmark) Denmark), 2016-05, Vol.17 (5), p.515-535
• Main Authors: Barrett, Alec, Hermann, Greg J.
• Format: Article
• Language: English
• Subjects: Animals; BEACH domain; Caenorhabditis elegans; Caenorhabditis elegans - metabolism; Endosomes - metabolism; Genes; lysosome; Lysosomes - metabolism; lysosome‐related organelle; LYST; Mutation; NBEAL2; Nematodes; Vesicular Transport Proteins - genetics; Vesicular Transport Proteins - metabolism
• ISSN: 1398-9219; 1600-0854
• DOI: 10.1111/tra.12381

LYST‐1 is a Caenorhabditis elegans BEACH domain containing protein (BDCP) homologous to LYST and NBEAL2, BDCPs controlling organelle biogenesis that are implicated in human disease. Unlike the three other BDCPs encoded by C. elegans, mutations in lyst‐1 lead to smaller lysosome‐related organelles (LROs), smaller lysosomes, increased numbers of LROs and decreased numbers of early endosomes. lyst‐1(−) mutations do not obviously disrupt protein trafficking to lysosomes or LROs, however, the formation of gut granules is diminished. While the trafficking pathways that mediate the delivery of proteins to lysosome‐related organelles (LROs) are becoming increasingly clear, how LRO size and numbers are controlled is relatively unstudied. BEACH domain containing proteins (BDCPs) have emerged as potential regulators of these processes. Caenorhabditis elegans lyst‐1 encodes a BDCP that is homologous to both human LYST, which is mutated in Chediak‐Higashi syndrome, and NBEAL2, which is mutated in gray platelet syndrome. We show that mutations in lyst‐1 lead to fragmentation of intestinal specific LROs called gut granules. Protein trafficking to gut granules appears to be unaffected in lyst‐1(−) mutants; however, gut granule formation and function is disrupted. We find that lysosomes are smaller in both intestinal cells and coelomocytes of lyst‐1(−) mutants. We show that mutations in the three other BDCPs encoded by C. elegans do not similarly alter gut granule morphology. While recycling and late endosomes appear to be unaltered, mutations in lyst‐1 cause a significant reduction in the number of RAB‐5::GFP containing early endosomes, an effect that has not been reported for any other BDCP mutant.