MPI for Heart and Lung Research
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Project leaders: Prof. Dr. Thomas Worzfeld, Dr. Remy Bonnavion

Technical Assistants: Daniel Heil, Dagmar Magalei


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.


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).


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