Abstract
The GTP-binding protein septin 7 is involved in various cellular processes, including cytoskeleton organization, migration and the regulation of cell shape. Septin 7 function in lymphocytes, however, is poorly characterized. Since the intracellular signaling role of septin 7 is dependent on its interaction network, interaction proteomics was applied to attain novel knowledge about septin 7 function in hematopoietic cells. Our previous finding of decreased septin 7 expression in blood-derived lymphocytes in ERU, a spontaneous animal model for autoimmune uveitis in man, extended the role of septin 7 to a potential key player in autoimmunity. Here, we revealed novel insights into septin 7 function by identification of DOCK8 as an interaction partner in primary blood-derived lymphocytes. Since DOCK8 is associated with important immune functions, our finding of significantly decreased DOCK8 expression and altered DOCK8 interaction network in ERU might explain changes in immune response and shows the contribution of DOCK8 in pathomechanisms of spontaneous autoimmune diseases. Moreover, our analyses revealed insights in DOCK8 function, by identifying the signal transducer ILK as a DOCK8 interactor in lymphocytes. Our finding of the enhanced enrichment of ILK in ERU cases indicates a deviant influence of DOCK8 on inter- and intracellular signaling in autoimmune disease.
Highlights
Septins are GTP-binding cytoskeletal proteins involved in various cellular processes, including cytokinesis, membrane dynamics and regulation of cell shape[1,2]
By comparing integrin-linked kinase (ILK) protein levels in lymphocytes of healthy and equine recurrent uveitis (ERU) cases, we detected a significant increase of ILK protein expression in primary blood-derived lymphocytes (PBL) of diseased specimen (Fig. 5A)
The aim of our study was to extend the knowledge about the role of septin 7 in lymphocytes and in the context of a spontaneous autoimmune disease
Summary
Septins are GTP-binding cytoskeletal proteins involved in various cellular processes, including cytokinesis, membrane dynamics and regulation of cell shape[1,2]. They are highly conserved from yeast to humans. Due to its pivotal role in the formation of septin filaments, the depletion of septin 7 leads to destabilization of the core septin cytoskeleton in mammalian cells[1]. ERU represents the only spontaneous model for autoimmune uveitis in humans[8] and is characterized by remitting painful attacks of the inner eye, caused by infiltration of immune cells[9], eventually leading to vision loss. Accession ENSECAP00000009522 ENSECAP00000001117 ENSECAP00000003324 ENSECAP00000014750 ENSECAP00000016002 ENSECAP00000016124 ENSECAP00000021088 ENSECAP00000001004 ENSECAP00000004638 ENSECAP00000008007 ENSECAP00000022415 ENSECAP00000017987 ENSECAP00000020433 ENSECAP00000010583 ENSECAP00000016084 ENSECAP00000010141 ENSECAP00000007199 ENSECAP00000018986 ENSECAP00000003203 ENSECAP00000015383
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
