RESUMEN
The presence of islet autoantibodies remains a reliable biomarker to identify individuals at high risk of developing type 1 diabetes. As such, these autoantibodies play a pivotal role in understanding the prodrome of diabetes and selecting individuals for both prevention and intervention clinical trials. Over the last few decades, studies have sought to investigate autoantibody prevalence after diabetes onset to better understand ongoing islet autoimmunity; however, many findings are contradictory, and little is known about factors that may influence autoantibody persistence. Generally, glutamate decarboxylase autoantibodies (GADAs) are the most prevalent autoantibodies after diagnosis, particularly in adults, whilst zinc transporter 8 autoantibodies (ZnT8A) prevalence declines more rapidly. However, when studies with islet autoantibody data at diagnosis are considered, it becomes clear that overall islet antigen-2 autoantibodies (IA-2A) tend to persist for longer than GADA or ZnT8A. In this review, we assess the major studies that have contributed to our understanding of autoantibody persistence after diabetes onset and what factors affect this. Islet autoantibodies may provide biomarkers for long-term ß-cell function and insights into how to prevent ongoing islet autoimmunity but larger studies collecting samples at and decades after diabetes onset are required to leverage the information they could provide.
Asunto(s)
Autoanticuerpos/inmunología , Autoinmunidad , Diabetes Mellitus Tipo 1/inmunología , Islotes Pancreáticos/inmunología , Biomarcadores/sangre , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiología , Salud Global , Humanos , Incidencia , Islotes Pancreáticos/metabolismoRESUMEN
In humans, MOZART1 plays an essential role in mitotic spindle formation as a component of the γ-tubulin ring complex. We report that the fission yeast homologue of MOZART1, Mzt1/Tam4, is located at microtubule-organizing centers (MTOCs) and coimmunoprecipitates with γ-tubulin Gtb1 from cell extracts. We show that mzt1/tam4 is an essential gene in fission yeast, encoding a 64-amino acid peptide, depletion of which leads to aberrant microtubule structure, including malformed mitotic spindles and impaired interphase microtubule array. Mzt1/Tam4 depletion also causes cytokinesis defects, suggesting a role of the γ-tubulin complex in the regulation of cytokinesis. Yeast two-hybrid analysis shows that Mzt1/Tam4 forms a complex with Alp6, a fission yeast homologue of γ-tubulin complex protein 3 (GCP3). Biophysical methods demonstrate that there is a direct interaction between recombinant Mzt1/Tam4 and the N-terminal region of GCP3(Alp6). Together our results suggest that Mzt1/Tam4 contributes to the MTOC function through regulation of GCP3(Alp6).