PgmNr W4176: Three conserved tetraspanin proteins positively modulate BMP signaling in C. elegans.

Authors:
Zhiyu Liu; Herong Shi; Jun Liu


Institutes
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853.


Keyword: Other ( signaling transduction )

Abstract:

The bone morphogenetic protein (BMP) signaling pathway plays essential roles in multiple developmental and homeostatic processes in metazoans. While the core BMP pathway members are well studied, much is needed for understanding the mechanisms involved in the spatiotemporal regulation of BMP signaling in vivo. We recently identified three highly conserved tetraspanin proteins, TSP-12, TSP-14 and TSP-21, as positive modulators of the BMP signaling pathway in C. elegans (Liu et al., 2015). tsp-21(0) single mutants or tsp-12(0); tsp-14(0) double mutants exhibit defects caused by reduced BMP signaling, including a small body size, reduced expression of a BMP signaling reporter, the RAD-SMAD reporter, and suppression of the mesodermal patterning defects of mutants in the C. elegans Schnurri homolog SMA-9. While all three tetraspanins are expressed and function in the signal-receiving cells to promote BMP signaling, TSP-21 appears to function in parallel with TSP-12 and TSP-14, because tsp-12(0); tsp-14(0) tsp-21(0) triple mutants are smaller than either tsp-21(0) single mutant or tsp-12(0); tsp-14(0) double mutant. We have found that TSP-21 is plasma-membrane localized and that this localization is not affected in tsp-12(0); tsp-14(0) double mutants. We are currently further dissecting the functional relationship among these three tetraspanin proteins. TSP-21 is orthologous to human TSPAN4, TSPAN9 and CD53. TSP-12 and TSP-14 are paralogous to each other and homologous to human TSPAN5, TSPAN10, TSPAN14, TSPAN15, TSPAN17 and TSPAN33. We speculate that these human tetraspanin proteins may also function in modulating BMP signaling.

Liu, Z et al. (2015) Promotion of Bone Morphogenetic Protein Signaling by Tetraspanins and Glycosphingolipids. PLoS Genetics 11(5):e1005221.



Wormbase Genetic Index
1. tsp-12
2. tsp-14
3. tsp-21
4. sma-9