The transmembrane LRR protein DMA-1 promotes dendrite branching and growth in C. elegans

Abstract

Dendrites often adopt complex branched structures. The development and organization of these arbors fundamentally determine the potential input and connectivity of a given neuron. The cell-surface receptors that control dendritic branching remain poorly understood. Here, we show that in Caenorhabditis elegans, a previously uncharacterized transmembrane protein containing extracellular leucine-rich repeat (LRR) domains, which we name DMA-1 (Dendrite-Morphogenesis-Abnormal), promotes dendrite branching and growth. Sustained expression of dma-1 is found only in the elaborately branched sensory neurons PVD and FLP. Genetic analysis showed that loss of dma-1 causes much reduced dendritic arbors while overexpression of dma-1 results in excessive branching. Forced expression of dma-1 in neurons with simple dendrites was sufficient to promote ectopic branching. Animals lacking dma-1 are defective in sensing harsh touch. DMA-1 is the first transmembrane LRR protein to be implicated in dendritic branching and expands the breadth of roles played by LRR receptors in nervous system development.

Sarcomeres Pattern Proprioceptive Sensory Dendritic Endings through UNC-52/Perlecan in C. elegans

“…Previous studies by Bulow’s group and ours showed that trans-membrane cell adhesion molecule SAX-7, together with a novel membrane protein MNR-1, function in the hypodermal cells to guide the growth and branching of the 2° and 3° branches (Dong et al, 2013; Liu and Shen, 2012; Salzberg et al, 2013). SAX-7 localized to two longitudinal stripes, which provided the growth and branching signal for PVD 3° dendrites (Fig.…”

“…The shape of menorah is likely instructed by receptor-ligand interactions between PVD and its environment. Our previous work showed that DMA-1, a trans-membrane LRR protein, is the essential receptor in PVD for patterning menorahs (Liu and Shen, 2012). DMA-1 senses hypodermal derived signals SAX-7/L1CAM and MNR-1 in a tripartite ligand-receptor complex, which spatially instructs the growth and branching of PVD dendrites (Dong et al, 2013; Salzberg et al, 2013).…”

AFF-1 fusogen can rejuvenate the regenerative potential of adult dendritic trees via self-fusion

“…1A) (Oren-Suissa et al, 2010). These dendritic trees arise and are dynamically maintained through several intrinsic and extrinsic genetic pathways (Chatzigeorgiou et al, 2010;Cohen et al, 2014;Dong et al, 2013Dong et al, , 2015Husson et al, 2012;Liu and Shen, 2011;Maniar et al, 2012;Oren-Suissa et al, 2010;Salzberg et al, 2013;Smith et al, 2010;Wei et al, 2015).…”

Regulation of dendrite morphogenesis by extrinsic cues

“…Consistent with its role in cell-cell fusion, EFF-1 mediates pruning through neurite-neurite fusion as well as branch retraction. Using the same model system, a function for the leucine-rich repeat transmembrane protein DMA-1 (dendrite-morphogenesis-abnormal 1) has been observed [73]. In contrast to EFF-1, knockdown of DMA-1 results in reduced dendrite branching, while overexpression triggers exuberant arborization.…”