![]() ![]() It is relevant to stress that a number of mutations in both OPTN and TBK1 have been identified in patients suffering from amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), which points toward an important role of the OPTN–TBK1 complex in autophagy and neurodegeneration ( 19– 22). Activity and specificity of TBK1 are defined by adaptor proteins these recruit TBK1 to microdomains on ubiquitinated Salmonella or mitochondria, thereby facilitating its local clustering and activation ( 18), where it in turn can phosphorylate autophagy receptors ( 15). ![]() TANK-binding kinase 1 (TBK1) phosphorylates OPTN on S177, thereby enhancing LC3-binding affinity and autophagic clearance of cytosolic Salmonella ( 15). The autophagy receptors optineurin (OPTN) and p62 are first activated by protein kinases to effectively target autophagic membranes or their polyUb cargo ( 15– 17). Thus, TBK1-mediated phosphorylation of autophagy receptors creates a signal amplification loop operating in selective autophagy of damaged mitochondria.Īutophagy receptors function as decoders for the various ubiquitin signals on cargoes, linking cargoes to autophagosomal membranes ( 4) however, the basis of their individual recruitment to cargo as well as their distinct and cooperative functions in cargo sequestration are still poorly understood. Moreover, phosphorylation of OPTN on S473 enables binding to pS65 Ub chains and is also implicated in PINK1-driven and Parkin-independent mitophagy. In combination with phosphorylation of S177 and S513, this posttranslational modification promotes recruitment and retention of OPTN/TBK1 on ubiquitinated, damaged mitochondria. TBK1 in turn phosphorylates OPTN’s UBAN domain at S473, thereby expanding the binding capacity of OPTN to diverse Ub chains. Constitutive interaction of TBK1 with OPTN and the ability of OPTN to bind to ubiquitin chains are essential for TBK1 recruitment and kinase activation on mitochondria. ![]() By using quantitative proteomics, we show that Tank-binding kinase 1 (TBK1) phosphorylates all four receptors on several autophagy-relevant sites, including the ubiquitin- and LC3-binding domains of OPTN and p62/SQSTM1 as well as the SKICH domains of NDP52 and TAX1BP1. The privately owned company announced its decision after police warned of an extra influx of 1,000 protesters for the coming weekend, illuminating the country’s escalating anti-fracking movement.Selective autophagy of damaged mitochondria requires autophagy receptors optineurin (OPTN), NDP52 (CALCOCO2), TAX1BP1, and p62 (SQSTM1) linking ubiquitinated cargo to autophagic membranes. In response to growing protests in Southern England, Cuadrilla Resources has suspended its oil drilling activity in the village of Balcombe, Reuters reported. “We are really in a race to get the infrastructure built,” said Public Utilities Director Patrick Wiemiller. #TETRA ENRICH TORRENT SERIES#The Fresno City Council voted yesterday for a series of water rate increases over the next four years, which will fund nearly $US 410 million worth of water related infrastructure projects, American Broadcast Company reported. The Ministry of Environment has plans to introduce regulation in the 2014 legislature sitting, however experts note that successive governments have been talking about modernizing water for decades and successful action has yet to be taken. Water demand is expected to exceed supply by 40 percent in 2030, Michael Zacka, President and CEO of Tetra Pak, writes in a blog post for The Huffington Post. While most companies have sophisticated and effective sustainability programs in place, he notes that water management often falls off radar into less obvious areas of concern.īritish Columbia’s lack of groundwater regulation has allowed Nestlé Waters Canada to extract nearly 265 million liters (70 million gallons) of water from the Fraser Valley each year for free, The Province reported. ![]()
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