#retromer

The complex interplay between TDP-43 loss of function, alternative polyadenylation (APA) changes, and retromer/endolysosomal dysfunction in FTLD-TDP. The authors' data support a model in which TDP-43 loss-of-function triggers APA changes in key transcripts, including the retromer core component VPS35, resulting in reduced VPS35 and VPS29 protein levels and, subsequently, retromer dysfunction. In turn, endolysosomal dysfunction diminishes TDP-43 degradation, exacerbating TDP-43 mislocalization and loss of function in TDP-43 proteinopathies. Created in BioRender. Maheswari Jawahar, V. (2025)

TDP-43 loss in frontotemporal #dementia (FTD) changes alternative polyA, but what are the consequences? This study shows that 3′UTR lengthening of VPS35 in #FTD patient brains correlates with reduced VPS35 & VPS29 levels, potentially inducing #retromer dysfunction @plosbiology.org 🧪 plos.io/49q3Db4

The complex interplay between TDP-43 loss of function, alternative polyadenylation (APA) changes, and retromer/endolysosomal dysfunction in FTLD-TDP. The authors' data support a model in which TDP-43 loss-of-function triggers APA changes in key transcripts, including the retromer core component VPS35, resulting in reduced VPS35 and VPS29 protein levels and, subsequently, retromer dysfunction. In turn, endolysosomal dysfunction diminishes TDP-43 degradation, exacerbating TDP-43 mislocalization and loss of function in TDP-43 proteinopathies. Created in BioRender. Maheswari Jawahar, V. (2025)

TDP-43 loss in frontotemporal #dementia (FTD) changes alternative polyA, but what are the consequences? This study shows that 3′UTR lengthening of VPS35 in #FTD patient brains correlates with reduced VPS35 & VPS29 levels, potentially inducing #retromer dysfunction @plosbiology.org 🧪 plos.io/49q3Db4

The complex interplay between TDP-43 loss of function, alternative polyadenylation (APA) changes, and retromer/endolysosomal dysfunction in FTLD-TDP. The authors' data support a model in which TDP-43 loss-of-function triggers APA changes in key transcripts, including the retromer core component VPS35, resulting in reduced VPS35 and VPS29 protein levels and, subsequently, retromer dysfunction. In turn, endolysosomal dysfunction diminishes TDP-43 degradation, exacerbating TDP-43 mislocalization and loss of function in TDP-43 proteinopathies. Created in BioRender. Maheswari Jawahar, V. (2025)

TDP-43 loss in frontotemporal #dementia (FTD) changes alternative polyA, but what are the consequences? This study shows that 3′UTR lengthening of VPS35 in #FTD patient brains correlates with reduced VPS35 & VPS29 levels, potentially inducing #retromer dysfunction @plosbiology.org 🧪 plos.io/49q3Db4

We next found that OXR1 is expressed with proteins in the endolysosomal network. By staining fly brains, we found that loss of OXR1 causes loss of proteins in the #retromer complex, like VPS35. The retromer takes cargo from endosomes and traffics them for reuse, as opposed to breakdown.