Biology subjects

Peterson, J. C.

Publications and source records attributed to Peterson, J. C..

4 recordsLinked to original sources

bioRxiv2025

Sorting endosomes play key roles in presentation of Mycobacterium tuberculosis-derived ligands to MAIT cells

The immune system has developed specialized mechanisms to recognize intracellular pathogens such as Mycobacterium tuberculosis (Mtb). Major Histocompatibility Complex Class I-Related molecule (MR1) is a conserved nonclassical antigen presenting molecule that presents ligands derived from microbial riboflavin synthesis to Mucosal Associated Invariant T (MAIT) cells. While endosomal trafficking facilitates MR1 antigen presentation during Mtb infection, the exact mechanisms by which MR1 loading of Mtb-derived ligands occurs are not known. We found that trafficking through sorting endosomes mediates MR1 antigen presentation during Mtb infection. Sorting endosomes utilize trafficking proteins such as Syntaxin 6, Syntaxin 12, Syntaxin 16 and VAMP4. Prior work demonstrates the importance of VAMP4 for MR1 presentation during Mtb infection; we have found that Stx12 and Stx16 are also important. Interference with Stx12 or Stx16 via siRNA-mediated knockdown reduces MR1 antigen presentation of Mtb. Using RFP-tagged constructs, we found Stx16 co-localized more with MR1 vesicles compared to Stx12 in MR1-GFP expressing airway epithelial cells. Stx12 and Stx16 blockade increase MR1 surface stabilization and total expression, indicating that impaired endosomal trafficking hinders MR1 internalization. Together, these findings support a role for sorting endosomes in the selective sampling of the intracellular environment and MR1-mediated recognition of Mtb-infected cells.

immunology↗

bioRxiv2025

Form and function of actin impacts actin health and aging.

The actin cytoskeleton is a fundamental and highly conserved structure that functions in diverse cellular processes, yet its direct contribution to organismal aging remains unclear. Here, we systematically interrogated how genetic and pharmacologic perturbations of actin structure and function influence lifespan and various hallmarks of aging in Caenorhabditis elegans. Whole-animal and tissue-specific knockdown of actin and key actin-binding proteins (ABPs) - arx-2 (Arp2/3), unc-60 (cofilin), and lev-11 (tropomyosin) - led to premature disruption of filament organization, reduced lifespan, and tissue-specific physiological defects. Bulk and single-nucleus RNA-sequencing revealed that ABP knockdowns elicited a strongly "aged" transcriptome. Actin dysfunction broadly exacerbated many age-associated phenotypes, including mitochondrial dysfunction, lipid dysregulation, loss of proteostasis, impaired autophagy, and intestinal barrier failure. Pharmacological destabilization with Latrunculin A mirrored genetic knockdowns, while mild stabilization with Jasplakinolide modestly extended lifespan, emphasizing that optimal and finely-tuned actin function is critical for healthy aging. Finally, analysis of human genome-wide association data revealed that common ACTB polymorphisms correlate with differences in age-related decline in gait speed, suggesting evolutionary conservation of actins role in healthy aging. Taken together, our results provide a comprehensive and publicly accessible resource that maps, for the first time, how actin integrity intersects with diverse aging pathways across tissues and scales. This descriptive framework is intended to enable future mechanistic discovery by offering a deep, unbiased dataset that can be integrated with emerging studies to define how actin dynamics contribute to aging.

cell biology↗

bioRxiv2025

Synaptotagmin 1 and Synaptotagmin 7 promote MR1-mediated presentation of Mycobacterium tuberculosis antigens

Mycobacterium tuberculosis (Mtb) is an intracellular pathogen that can be sensed by T cells, which are essential for the control of infection. In comparison to viral infections, Mtb antigens are relatively limited and hence, challenging to sample. Specialized antigen presentation pathways enable the presentation of such scarce antigens to CD8+ T cells, which are, thus, uniquely poised to survey intracellular environments. A subset of CD8+ T cells prevalent in the airways, known as mucosal-associated invariant T (MAIT) cells, can be activated through the presentation of Mtb antigens via the MHC class I-related protein 1 (MR1) molecule. Prior work demonstrates that endosomal calcium signaling is critical for MR1-mediated presentation of Mtb-derived antigens. Here, we show that the calcium-sensing trafficking proteins Synaptotagmin (Syt) 1 and Syt7 specifically promote MAIT cell activation in response to Mtb-infected cells. In bronchial epithelial cells, Syt1 and Syt7 localize to late endo-lysosomes and MR1 vesicles. Loss of Syt1 and Syt7 results in enlarged MR1 vesicles and an increased number of MR1 vesicles in close proximity to Mtb-containing vacuoles during infection. This study identifies a specialized pathway in which Syt1 and Syt7 facilitate the translocation of MR1 from Mtb-containing vacuoles, potentially to the cell surface for antigen presentation.

immunology↗

bioRxiv2020

Pulmonary ductal coarctation and left pulmonary artery interruption; pathology and role of neural crest and second heart field during development

ObjectivesIn congenital heart malformations with pulmonary stenosis to atresia an abnormal lateral ductus arteriosus to left pulmonary artery connection can lead to a localised narrowing (pulmonary ductal coarctation) or even interruption We investigated embryonic remodelling and pathogenesis of this area. Material and methods. Normal development was studied in WntCre reporter mice (E10.0-12.5) for neural crest cells and Nkx2.5 immunostaining for second heart field cells. Data were compared to stage matched human embryos and a VEGF120/120 mutant mouse strain developing pulmonary atresia. ResultsNormal mouse and human embryos showed that the mid-pharyngeal endothelial plexus, connected side-ways to the 6th pharyngeal arch artery. The ventral segment formed the proximal pulmonary artery. The dorsal segment (future DA) was solely surrounded by neural crest cells. The ventral segment had a dual outer lining with neural crest and second heart field cells, while the distal pulmonary artery was covered by none of these cells. The asymmetric contribution of second heart field to the future pulmonary trunk on the left side of the aortic sac (so-called pulmonary push) was evident. The ventral segment became incorporated into the pulmonary trunk leading to a separate connection of the left and right pulmonary arteries. The VEGF120/120 embryos showed a stunted pulmonary push and a variety of vascular anomalies. SummarySide-way connection of the DA to the left pulmonary artery is a congenital anomaly. The primary problem is a stunted development of the pulmonary push leading to pulmonary stenosis/atresia and a subsequent lack of proper incorporation of the ventral segment into the aortic sac. Clinically, the aberrant smooth muscle tissue of the ductus arteriosus should be addressed to prohibit development of severe pulmonary ductal coarctation or even interruption of the left pulmonary artery.

developmental biology↗