Show simple item record

Files in this item


There are no files associated with this item.

Item metadata

dc.contributor.advisorSleeman, Judith Elizabeth
dc.contributor.authorThompson, Luke
dc.coverage.spatialxxviii, 292 p.en_US
dc.description.abstractSpinal Muscular Atrophy (SMA) is a neurodegenerative, inherited disease caused by an insufficient amount of functional Survival of Motor Neurone protein (SMN), though the exact mechanism underlying this is not fully understood. The primary function of SMN is assembling a ring of Sm proteins around small nuclear RNA (snRNA) in an early, cytoplasmic stage of small nuclear ribonucleoprotein (snRNP) biogenesis, a process essential in eukaryotes. SMN, together with several mRNA binding proteins, has been linked to neural transport of mRNA towards areas of growth in Motor neurons for local translation of transcripts. Previous research in our group has found that this may involve Coatomer protein-containing vesicles transported by Dynein and requiring the Sm family protein, SmB, for maintenance. Little is known, however, about what other proteins are also present and required for correct transport and localisation of these vesicles. To further investigate this, we have produced plasmids expressing each Sm protein tagged to fluorescent proteins to help track their behaviour, in some cases for the first time, and developed a detergent-free fractionation protocol to enrich for SMN containing vesicles, providing tools that can be used to further probe behaviour and interactions in the future. Using these approaches, SmN, a neural specific Sm protein, was identified to also be present in SMN-containing vesicles similarly to SmB. Analysis of the interactomes of different Sm proteins identified a novel interactor of SMN, Neurochondrin (NCDN), that appears to be required for the correct localisation of SMN in neural cells. NCDN was found to not associate with snRNPs, indicating an snRNP-independent interaction with SMN. NCDN and SMN both independently associated and co-enriched with Rab5, indicating a potential endocytic and cell polarity role for the interaction. This interaction has the potential to be key in SMA pathology and may have therapeutic potential.en_US
dc.publisherUniversity of St Andrews
dc.subjectSpinal Muscular Atrophyen_US
dc.subjectSmall nuclear ribonucleoproteinen_US
dc.subjectVesicle transporten_US
dc.subjectSm Proteinen_US
dc.subject.lcshProtein-protein interactionsen
dc.subject.lcshSpinal muscular atrophyen
dc.titleThe identification and investigation of neurochondrin as a novel interactor of the survival of motor neuron protein, through analysis of the interactomes of Sm family proteins and cell fractionationen_US
dc.contributor.sponsorMedical Research Council (MRC)en_US
dc.type.qualificationnamePhD Doctor of Philosophyen_US
dc.publisher.institutionThe University of St Andrewsen_US
dc.rights.embargoreasonThesis restricted in accordance with University regulations. Print and electronic copy restricted until 13th March 2020en

This item appears in the following Collection(s)

Show simple item record