Functional Characterisation of Syndecan, a heparan sulpahte proteoglycan, in Slit/Robo signalling

Functional Characterisation of Syndecan, a heparan sulpahte proteoglycan, in Slit/Robo signalling

Funktionale Charakterisierung von Syndecan, ein Heparansulfatproteoglykan, im Slit/Robo-Signalweg

Bhavna Chanana

Doctoral thesis

Date of Examination: 2007-11-06

Date of issue: 2008-04-25

Advisor: Vorbrüggen, Gerd Dr.

Referee: Vorbrüggen, Gerd Dr.

Referee: Wimmer, Ernst A. Prof. Dr.

Referee: Pieler, Tomas Prof. Dr.

Persistent Address: http://hdl.handle.net/11858/00-1735-0000-000D-F150-F

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Abstract

English

Syndecan (Sdc) is a type I transmembrane protein characterized by the presence of linear sugar chains called heparan sulphate glycosaminoglycans (HSGAGs) linked to its extracellular domain. Sdc was shown to be critical for the fidelity of Slit repellent signalling at the Drosophila midline where via its receptor Robo, Slit patterns the central nervous system (CNS) and the musculature. This study aimed at shedding some light on how Sdc functions in Slit/Robo signalling. Employing the UAS/GAL4 system, different sdc variants and chimeric transgenes were expressed in specific tissues in a sdc mutant background and tested for their rescue capability. Rescue was scored by the absence of ventral midline crossing of ipsilateral axons and ventral muscles. The in vivo rescue experiments proved that Drosophila Sdc is specifically required on the target tissue where it functions as a coreceptor with Robo and that Sdc has no function in Slit secretion or transport nor does it have an independent intracellular signalling activity. Furthermore, the results also support a model in which shedding of Sdc though not required for the fidelity of Slit repellent signalling could occur by the proteolytic activity of a serine protease which might function as a negative feedback system or might be required for the recycling of Robo receptor.

Keywords: Syndecan; heparan sulphate proteoglycan; Slit; Robo; axon guidance

Other Languages

Syndecan (Sdc) ist ein Transmembranprotein der Klasse I, das im Bereich seiner extrazellulären Domäne mit mehreren linearen Zuckerketten modifiziert ist. Diese Zuckerketten werden als Heparansulfat-Glykosaminoglykane (HSGAG) bezeichnet. In vorhergehenden Experimenten konnte eine essentielle Funktion des Sdc-Proteins für die Slit-Signaltransduktion an der Mittellinie des Drosophila Embryos gezeigt werden. Das sezernierte Slit-Protein über die Bindung an den Robo-Rezeptor als abstoßende Aktivität, die sowohl die Axone des zentralen Nervensystems (ZNS) als auch die Muskulatur im ventralen Bereich des Embryos strukturiert. Die vorliegende Doktorarbeit hatte das Ziel, ein besseres Verständnis der Funktion des Sdc-Proteins innerhalb des Slit/Robo-Signaltransduktionsweges zu gewinnen. Mit Hilfe des UAS/GAL4-Systems wurden verschiedene Sdc-Proteinvarianten und Protein

Schlagwörter: Syndecan; Heparansulfatproteoglykan; Slit; Robo; Axone