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Guzman, J.

Publications and source records attributed to Guzman, J..

2 recordsLinked to original sources

Dynamic Response in the Larval Geoduck Clam Proteome to Elevated pCO2

Pacific geoduck clams (Panopea generosa) are found along the Northeast Pacific coast where they are significant components of coastal and estuarine ecosystems and the basis of a growing and highly profitable aquaculture industry. The Pacific coastline, however, is also the sight of rapidly changing ocean habitat, including significant reductions in pH. The impacts of ocean acidification on invertebrate bivalve larvae have been widely documented and it is well established that many species experience growth and developmental deficiencies when exposed to low pH. As a native of environments that have historically lower pH than the open ocean, it is possible that geoduck larvae are less impacted by these effects than other species. Over two weeks in larval development (days 6-19 post-fertilization) geoduck larvae were reared at pH 7.5 or 7.1 in a commercial shellfish hatchery. Larvae were sampled at six time points throughout the period for a in-depth proteomics analysis of developmental molecular physiology. Larvae reared at low pH were smaller than those reared at ambient pH, especially in the prodissoconch II phase of development. Competency for settlement was also delayed in larvae from the low pH conditions. A comparison of proteomic profiles over the course of development reveal that these differing phenotypic outcomes are likely due to environmental disruptions to the timing of molecular physiological events as suites of proteins showed differing profiles of abundance between the two pH environments. Ocean acidification likely caused an energetic stress on the larvae at pH 7.1, causing a shift in physiological prioritization with resulting loss of fitness.

molecular biology

PIKfyve deficiency in myeloid cells impairs lysosomal homeostasis in macrophages and promotes systemic inflammation in mice

Macrophages are professional phagocytes that are essential for host defense and tissue homeostasis. Proper membrane trafficking and degradative functions of the endolysosomal system is known to be critical for the function of these cells. We have found that PIKfyve, the kinase that synthesizes the endosomal phosphoinositide PI(3,5)P2, is an essential regulator of lysosomal biogenesis and degradative functions in macrophages. Genetically engineered mice lacking PIKfyve in their myeloid cells (PIKfyvefl/fl LysM-Cre) develop diffuse tissue infiltration of foamy macrophages, hepatosplenomegaly, and systemic inflammation. PIKfyve loss in macrophages causes enlarged endolysosomal compartments and impairs the lysosomal degradative function. Moreover, PIKfyve deficiency increases the cellular levels of lysosomal proteins. Although PIKfyve deficiency reduced the activation of mTORC1 pathway and was associated with increased cleavage of TFEB proteins, this does not translate into transcriptional activation of lysosomal genes, suggesting that PIKfyve modulates the abundance of lysosomal proteins by affecting the degradation of these proteins. Taken together, our study shows that PIKfyve modulation of lysosomal degradative activity and protein expression is essential to maintain lysosomal homeostasis in macrophages.

cell biology