Xing Liang

Stanford University; Stanford CA, United States of America

Liang, Xing et al. (2021) International Worm Meeting "Growth Cone-Localized Microtubule Organizing Center Establishes Microtubule Orientation in Dendrites"

Feldman, Jessica, Fetter, Richard, Kokes, Marcela, Liang, Xing, Shen, Kang, Sallee, Maria, Moore, Adrian

[International Worm Meeting, 2021]

A polarized arrangement of neuronal microtubule arrays is the foundation of membrane trafficking and subcellular compartmentalization. Conserved among both invertebrates and vertebrates, axons contain exclusively "plus-end-out" microtubules while dendrites contain a high percentage of "minus-end-out" microtubules, the origins of which have been a mystery. Here we show that in Caenorhabditis elegans the dendritic growth cone contains a non-centrosomal microtubule organizing center, which generates minus-end-out microtubules along outgrowing dendrites and plus-end-out microtubules in the growth cone. RAB-11-positive endosomes accumulate in this region and co-migrate with the microtubule nucleation complex gamma-TuRC. The MTOC tracks the extending growth cone by kinesin-1/UNC-116-mediated endosome movements on distal plus-end-out microtubules and dynein clusters this advancing MTOC. Critically, perturbation of the function or localization of the MTOC causes reversed microtubule polarity in dendrites. These findings unveil the endosome-localized dendritic MTOC as a critical organelle for establishing axon-dendrite polarity.

Xing-Jie Liang

National Center for Nanoscience and Technology of China; Beijing, China

MAH547

Caenorhabditis elegans

Jiang N et al. (2015) Dev Cell "Muscles get dendrites into shape."

Jiang N, Parrish JZ

[Dev Cell, 2015]

Sensory neurons interact with muscles in many contexts, but muscle-derived signals that pattern sensory dendrites have not been extensively characterized. In this issue of Developmental Cell, Liang etal. (2015) report a signaling system in which positional cues from muscle are transduced to hypodermal cells to direct sensory dendrite outgrowth.

CE541

Caenorhabditis elegans

Ubxn4

Homo sapiens

UBXD2 is an integral membrane protein of the endoplasmic reticulum (ER) that binds valosin-containing protein (VCP; MIM 601023) and promotes ER-associated protein degradation (ERAD) (Liang et al., 2006 [PubMed 16968747]).[supplied by OMIM, Mar 2008]

Zou, Wei et al. (2017) International Worm Meeting "HPO-30/Claudin forms a co-receptor complex with DMA-1 to promote dendritic branching in C. elegans PVD neurons."

Broederdorf, Timothy, Shen, Kang, Zou, Wei, Liang, Xing, Shen, Ao, Xiang, Kevin, Dong, Xintong, Chen, Baoyu

[International Worm Meeting, 2017]

Dendrite morphogenesis is a critical step for neural circuit assembly. However, the underlying molecular mechanisms are still not fully understood. Previous studies by others and us have identified a receptor-ligand complex, which includes DMA-1, SAX-7, MNR-1 and LECT-2, guides the branching and growth of C. elegans PVD dendrites. Here we found that HPO-30, a claudin-like protein, forms a co-receptor complex with DMA-1 in PVD dendrites to regulate dendritic branching. Genetically hpo-30 functions in a same pathway with dma-1, and dma-1 over-expression can partially bypass the requirement of HPO-30. HPO-30 interacts with DMA-1 both in vitro and in vivo. Using single-molecule pull-down assays, we found that HPO-30 forms a multi-protein complex with DMA-1, SAX-7, MNR-1 and LECT-2, but is not required for the interaction between DMA-1 and the ligand complex. Importantly, the cytosolic domain of HPO-30 interacts with the WAVE regulatory complex to promote dendritic branching. Meanwhile, the cytosolic domain of DMA-1 interacts with TIAM-1/RacGEF and is required for the formation of dendritic branches. Together, our study revealed that HPO-30 and DMA-1 form a novel co-receptor complex to promote robust dendritic branch formation by regulating local actin assembly.

Edlira Yzeiraj et al. (2007) International Worm Meeting "Regulation and expression of collagens and fat metabolism genes in the dbl-1 pathway."

Dr. Cathy Savage-Dunn, Edlira Yzeiraj, Mariya Fabisevich

[International Worm Meeting, 2007]

In C. elegans DBL-1 is a member of the TGF-<font face=symbol>b</font> superfamily closely related to Drosophila Dpp and vertebrate BMP-2/BMP-4 (Suzuki et al., 1999, Development 126, 241-250). The DBL-1 signaling pathway regulates body size and patterning of male-specific copulatory structures. In regulating body size DBL-1 acts as a dosage-dependent regulator (Suzuki et al., 1999). Loss of dbl-1 activity results in smaller animals, while overexpression of dbl-1 results in longer animals. From microarray analysis 242 genes regulated by dbl-1 were identified. From these, 159 genes are repressed but only 83 genes are activated (Liang et al., 2007, Developmental Biology, In Press). We are interested in determining the biological function of some of these putative target genes. We are focusing on collagens and genes involved in fat metabolism. Collagen genes are involved in body size regulation. Cuticle collagens are synthesized by the hypodermis and secreted on the surface of the worm body as an exoskeleton. In the C. elegans genome, about 175 genes encode collagen-like polypeptides. Mutation of these genes causes defects in body morphogenesis, e.g. dumpy, roller, blister, and embryonic lethality (Myllyharju and Kivirikko, 2004, Trends Genet. 20, 33-43). From the microarray analyses three collagen genes were identified as dbl-1-regulated target gene, col-141, rol-6 and col-41. It is believed that dbl-1 represses col-141 and activates rol-6 and col-41 (Liang et. al., 2007). We plan to confirm the gene regulation of these genes by initially performing RT-PCR and then do RNAi to test their function. We are also focusing on genes involved in fat metabolism and transport, specifically vit-5, vit-6, fat-6, fat-7, and ins-7 (Liang et. al., 2007). We are interested in whether the dbl-1 pathway regulates body size in part by regulation of fat storage and metabolism. In addition these genes are believed to play a key role in C. elegans aging. vit-5, vit-6, and ins-7 are upregulated by the dbl-1 pathway, and fat-6 and fat-7 are downregulated by it, and this regulation has been confirmed by RT-PCR for some of these genes. To examine these genes we will use fat staining, GFP-reporters, and RNAi feeding. During the fat staining procedure, worms ingest fluorescent particles, which are temporarily stored in the intestinal cells. The cells can then be seen under a fluorescent microscope, and analyzed for number and degree of fat content. GFP reporters will be used on fat-6, fat-7 and ins-7 to locate the physical expression of the gene.

Kcnma1

Homo sapiens

This gene encodes the alpha subunit of calcium-activated BK channel. The encoded protein is involved in several physiological processes including smooth muscle contraction, neurotransmitter release and neuronal excitability. Mutations in this gene are associated with a spectrum of neurological disorders including Paroxysmal Nonkinesigenic Dyskinesia 3, Idiopathic Generalized Epilepsy 16 and Liang-Wang syndrome. [provided by RefSeq, Aug 2022]