Septins, a Novel Group of GTP-binding Proteins – Relevance in Hemostasis, Neuropathology and Oncogenesis

 

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Abstract

Septins are a novel family of GTP-binding proteins which are essential for cytokinesis, vesicle trafficking, cytoskeletal reorganization and membrane dynamics. They are abundantly expressed in many mitotic cells. Interestingly, they are also expressed in non-dividing cells such as neurons and platelets in which they play an important role in exocytosis. Platelets from SEPT5 knockout mice show an enhanced serotonin secretion and platelet aggregation in response to subthreshold levels of agonists. Septins are associated with a wide array of critical biological events such as neoplasia, neurodegenerative diseases, infections and exocytosis. The role of septins in oncogenesis is complex. Increased expression of some septins seems to trigger the growth of tumor cells. However, other septin isoforms are shown to promote apoptosis and function as tumor suppressor proteins. Interestingly, septins form complexes consisting of multiple septin polypeptides and assemble into filaments and ring-like, higher-order structures. The different septins and their various isoforms seem to determine the function of the septin complex.

Zusammenfassung

Septine bilden eine neue Familie GTP-bindender Proteine, die für Zytokinese, intrazellulären Vesikeltransport, Organisation des Zytoskeletts und Membranveränderungen essentiell sind. Sie werden in vielen sich schnell-teilenden Zellen wie auch in sich nicht-teilenden Zellen exprimiert und sind hier für die Exozytose wichtig. Septine sind in vielfältige wichtige zellbiologische Prozesse involviert wie z.B. Onkogenese, neurodegenerative Erkrankungen, Infektionen und Exozytose. Die Rolle der Septine in der Onkogenese ist komplex. Erhöhte Expression einiger Septine scheint das Tumorwachstum zu triggern. Jedoch fördern andere Septin-Isoformen die Apoptose und funktionieren als Tumorsuppressor-Proteine. Interessant ist, dass Septine Komplexe bilden, die aus mehreren Septinproteinen bestehen und die dann wiederum Filamente oder ringähnliche Strukturen bilden. Die unterschiedlichen Septine und ihre Isoformen scheinen die Funktion der verschiedenen Septinkomplexe zu bestimmen.

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Correspondence

Dr. K. Sandrock

University Hospital Freiburg

Department of Pediatrics and Adolescent Medicine

Mathildenstr.1

79106 Freiburg i. Br.

Germany

Phone: +49/761/270 71 93

Fax: +49/761/270 45 82

Email: kirstin.sandrock@uniklinik-freiburg.de