Semaphorin-plexin signaling

Project leaders: Dr. Remy Bonnavion
Technical Assistants: Daniel Heil, Dagmar Magalei

Work in this research area has focused on plexins of the B-family. Currently, new cellular mechanisms of plexin signaling as well as cell-type specific in vivo functions of particular semaphorin plexin pairs are analyzed. Recently, a role of plexin-B1 in mediating the prometastatic effects of ErbB-2 (Worzfeld et al, 2012) and of B-family plexins in the regulation of epithelial polarity have been discovered (Xia et al, 2015).

The mammalian semaphorin-plexin-system. Both semaphorins and their receptors, plexins, are characterized by the Sema domain which contains a seven-blade β-propeller. Mammalian semaphorins fall into five classes. Class 3 semaphorins (A-G) are soluble proteins, class 4 (A-D), 5 (A,B) and 6 (A-D) semaphorins are transmembrane proteins, and the class 7 semaphorin 7A is linked to the plasma membrane by a GPI anchor. Nine plexins have been described so far. Based on homology plexins are grouped into four subfamilies A,B,C and D. The cytoplasmic moieties of plexins (~600 amino acids) are highly conserved and do not show homology to any other known protein. Only B-plexins carry a PDZ binding motif. — **The mammalian semaphorin-plexin-system.** Both semaphorins and their receptors, plexins, are characterized by the Sema domain which contains a seven-blade β-propeller. Mammalian semaphorins fall into five classes. Class 3 semaphorins (A-G) are soluble proteins, class 4 (A-D), 5 (A,B) and 6 (A-D) semaphorins are transmembrane proteins, and the class 7 semaphorin 7A is linked to the plasma membrane by a GPI anchor. Nine plexins have been described so far. Based on homology plexins are grouped into four subfamilies A,B,C and D. The cytoplasmic moieties of plexins (~600 amino acids) are highly conserved and do not show homology to any other known protein. Only B-plexins carry a PDZ binding motif.

**The mammalian semaphorin-plexin-system.** Both semaphorins and their receptors, plexins, are characterized by the Sema domain which contains a seven-blade β-propeller. Mammalian semaphorins fall into five classes. Class 3 semaphorins (A-G) are soluble proteins, class 4 (A-D), 5 (A,B) and 6 (A-D) semaphorins are transmembrane proteins, and the class 7 semaphorin 7A is linked to the plasma membrane by a GPI anchor. Nine plexins have been described so far. Based on homology plexins are grouped into four subfamilies A,B,C and D. The cytoplasmic moieties of plexins (~600 amino acids) are highly conserved and do not show homology to any other known protein. Only B-plexins carry a PDZ binding motif.

Literature

Vogler M, Oleksy A, Schulze S, Fedorova M, Kojonazarov B, Nijjar S, Patel S, Jossi S, Sawmynaden K, Henry M, Brown R, Matthews D, Offermanns S, Worzfeld T. (2022) An antagonistic monoclonal anti-Plexin-B1 antibody exerts therapeutic effects in mouse models of postmenopausal osteoporosis and multiple sclerosis. J Biol Chem. 22 July 2022, 102265 [epub ahead of print]
Xia J, Swiercz JM, Bañón-Rodríguez I, Sun T, Frederico G, Matkovic I, Franz T, Brakebusch CH, Kumanogoh A, Friedel RH, Martín-Belmonte F, Gröne HJ, Offermanns S, Worzfeld T. (2015) Semaphorin-plexin signaling controls mitotic spindle orientation during epithelial morphogenesis and repair. Dev. Cell 33, 299-313
Worzfeld T, Offermanns S. (2014) Semaphorins and plexins as therapeutic targets. Nat. Rev. Drug Discov. 13, 603-21
Worzfeld T, Swiercz JM, Sentürk A, Genz B, Korostylev A, Deng S, Xia J, Hoshino M, Epstein JA, Chan AM, Vollmar B, Acker-Palmer A, Kuner R, Offermanns S. (2014) Genetic dissection of plexin signaling in vivo. Proc. Natl. Acad. Sci. U. S. A. 111, 2194-9
Worzfeld T, Swiercz JM, Looso M, Straub BK, Sivaraj KK, Offermanns S. (2012) ErbB-2 signals through Plexin-B1 to promote breast cancer metastasis. J. Clin. Invest. 122, 3296-2305