Imrie, L. | bioRxiv Science

bioRxiv2019

Trichoplein controls endothelial cell function by regulating autophagy

Autophagy is an essential cellular quality control process that emerged critical for vascular homeostasis. Here we describe, the role for Trichoplein (TCHP) protein in linking autophagy with endothelial cells (ECs) function. The depletion of TCHP in ECs impairs migration and sprouting. TCHP directly binds PCM1, to regulate degradation of GABARAP, thus leading to a defective autophagy. Mechanistically, TCHP is indispensable for autophagosome maturation and its depletion resulted in the accumulation of SQSTM1/p62 (p62) and unfolded protein aggregates in ECs. The latter process is coupled to TCHP-mediated NF-kB activation. Of note, low levels of TCHP and high p62 levels were detected in primary ECs from patients with coronary artery disease. In addition, Tchp knock-out mice showed accumulation of p62 in the heart and cardiac vessels and reduced cardiac vascularization. Here, we reveal an autophagy-mediated mechanism for TCHP down-regulation, which poses a plausible target for regulation of endothelial function.

molecular biology↗

bioRxiv2019

Shotgun proteomics analysis of nanoparticle-synthesising Desulfovibrio alaskensis in response to platinum and palladium

Platinum and palladium are much sought-after metals of global critical importance in terms of abundance and availability. At the nano-scale these metals are of even higher value due to their catalytic abilities for industrial applications. Desulfovibrio alaskensis is able to capture ionic forms of both of these metals, reduce them, and synthesize elemental nanoparticles. Despite this ability very little is known about the biological pathways involved in the formation of these nanoparticles. Proteomic analysis of D. alaskensis in response to platinum and palladium has highlighted those proteins involved in both the reductive pathways and the wider stress-response system. A core set of 13 proteins was found in both treatments and consisted of proteins involved in metal transport and reduction. There were also 7 proteins specific to either platinum or palladium. Over-expression of one of these platinum-specific genes, a NiFe hydrogenase small subunit (Dde_2137), resulted in the formation of larger nanoparticles. This study improves our understanding of the pathways involved in the metal resistance mechanism of Desulfovibrio and informs how we can tailor the bacterium for nanoparticle production, enhancing its application as a bioremediation tool and as way to capture contaminant metals from the environment. ImportanceBacteria, in particularly D. alaskensis, represent a biological and greener way to capture high value metals such as platinum group metals from environmental and industrial waste streams. The recovery of these metals in nanoparticle forms adds extra value to this process as they can be used in a variety of different industrial applications as they have exceptional catalytic capabilities. D. alaskensis ability to do this, has been widely reported, though very little is understood about the underlying protein and genetic components. It is by understanding the biological basis of this capability that we can further improve and adapt this bacterium to be better at bioremediation and to control its ability to do so.

microbiology↗