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Vesicular trafficking in osteoblasts

Prele, Cecilia M. A.; (2001) Vesicular trafficking in osteoblasts. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Secretion of bone matrix proteins is highly directional. Osteoblasts secrete newly synthesised bone matrix proteins towards the bone surface and away from neighbouring capillaries. The mechanisms responsible for this polarised secretion in osteoblasts have not yet been elucidated. Using the rat osteosarcoma cell line ROS17/2.8 and primary osteoblast-like cells derived from embryonic rat calvaria, we established that osteoblastic cells express a number of protein components implicated in apical junction complex formation. We therefore propose that osteoblasts may distinguish their apical and basolateral domains through the formation of these intercellular communicating pathways. Subsequently, we identified the expression of the general fusion machinery proteins, α-SNAP and NSF, in osteoblasts and determined v- and t-SNARE expression in these cells, with the particular aim of identifying components of the protein machinery which may be responsible for directing the exit of newly synthesised bone matrix proteins. We have demonstrated that osteoblastic cells express two splice variants of the v-SNARE VAMP1, rVAMP1B and VAMP1-OB, which localise to the cell cytoplasm in a vesicular manner, partially co-localising with transported matrix proteins, osteocalcin and collagen. Furthermore we identified the expression of synaptotagmins, a large family of specialised v-SNAREs that modulate calcium sensitivity of vesicular trafficking. Thus, osteoblasts may maintain a calcium sensitive exocytosis machinery, possibly under the influence of osteotropic hormones, in addition to their pathway of constitutive exocytosis. These data provide evidence that directionality of vesicular transport in osteoblasts involves junction complex formation and the SNARE proteins, rVAMP1B and VAMP1-OB.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Vesicular trafficking in osteoblasts
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Intercellular communicating pathways
URI: https://discovery.ucl.ac.uk/id/eprint/10107131
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