Biology subjects

Ying, G.

Publications and source records attributed to Ying, G..

5 recordsLinked to original sources

bioRxiv2024

Deciphering the chemical landscape and potential ecological function of RiPPs from the untapped Archaea domain

Chemical communication is crucial in ecosystems with complex microbial communities. However, the difficulties inherent to the cultivation of archaea have led to a limited understanding of their chemical language, especially regarding the structure diversity and function of secondary or specialized metabolites (SMs). Our comprehensive investigation into the biosynthetic potential of archaea, combined with metabolic analyses and the first report of heterologous expression in archaea, has unveiled the previously unexplored biosynthetic capabilities and chemical diversity of archaeal ribosomally synthesized and post-translationally modified peptides (RiPPs). We have identified twenty-four new lanthipeptides of RiPPs exhibiting unique chemical characteristics, including a novel subfamily featuring an unexplored type with diamino-dicarboxylic (DADC) termini, largely expanding the chemical landscape of archaeal SMs. This sheds light on the chemical novelty of archaeal metabolites and emphasizes their potential as an untapped resource for natural product discovery. Additionally, archaeal lanthipeptides demonstrate specific antagonistic activity against haloarchaea, mediating the unique biotic interaction in the halophilic niche. Furthermore, they showcase a new ecological role of RiPPs in enhancing the hosts motility by inducing the rod-shaped cell morphology and upregulating the archaellin gene expression, facilitating the archaeal interaction with abiotic environments. These discoveries broaden our understanding of archaeal chemical language and provide promising prospects for future exploration of SM-mediated interaction. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/616454v2_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@3647e4org.highwire.dtl.DTLVardef@1a9ebb1org.highwire.dtl.DTLVardef@b0efdeorg.highwire.dtl.DTLVardef@53d933_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2023

NUDC is critical for rod photoreceptor function, maintenance, and survival

NUDC (nuclear distribution protein C) is a mitotic protein involved in nuclear migration and cytokinesis across species. Considered a cytoplasmic dynein (henceforth dynein) cofactor, NUDC was shown to associate with the dynein motor complex during neuronal migration. NUDC is also expressed in postmitotic vertebrate rod photoreceptors where its function is unknown. Here, we examined the role of NUDC in postmitotic rod photoreceptors by studying the consequences of a conditional NUDC knockout in mouse rods (rNudC-/-). Loss of NUDC in rods led to complete photoreceptor cell death at six weeks of age. By 3 weeks of age, rNudC-/- function was diminished, and rhodopsin and mitochondria were mislocalized, consistent with dynein inhibition. Levels of outer segment proteins were reduced, but LIS1 (lissencephaly protein 1), a well-characterized dynein cofactor, was unaffected. Transmission electron microscopy revealed ultrastructural defects within the rods of rNudC-/- by 3 weeks of age. We investigated whether NUDC interacts with the actin modulator cofilin 1 (CFL1) and found that in rods, CFL1 is localized in close proximity to NUDC. In addition to its potential role in dynein trafficking within rods, loss of NUDC also resulted in increased levels of phosphorylated CFL1 (pCFL1), which would purportedly prevent depolymerization of actin. Absence of NUDC also induced an inflammatory response in Muller glia and microglia across the neural retina by 3 weeks of age. Taken together, our data illustrate the critical role of NUDC in actin cytoskeletal maintenance and dynein-mediated protein trafficking in a postmitotic rod photoreceptor. Significance StatementNuclear distribution protein C (NUDC) has been studied extensively as an essential protein for mitotic cell division. In this study, we discovered its expression and role in the postmitotic rod photoreceptor cell. In the absence of NUDC in mouse rods, we detected functional loss, protein mislocalization, and rapid retinal degeneration consistent with dynein inactivation. In the early phase of retinal degeneration, we observed ultrastructural defects and an upregulation of inflammatory markers suggesting additional, dynein-independent functions of NUDC.

cell biology↗

bioRxiv2022

Deletion of CEP164 in mouse photoreceptors post-ciliogenesis interrupts ciliary intraflagellar transport (IFT)

Centrosomal protein 164 (CEP164) is located at the edge of distal appendages in primary cilia and is necessary for basal body (BB) docking to the apical membrane. To investigate the function of CEP164 before and after BB docking in photoreceptors, we deleted CEP164 during retina embryonic development (Six3Cre), in postnatal rod photoreceptors (iCre75) and in mature retina using tamoxifen induction. BBs dock to the cell cortex during postnatal day 6 (P6) and extend a connecting cilium (CC) and an axoneme. P6 retina-specific knockouts (retCep164-/-) are unable to dock BBs, thereby preventing formation of a CC or outer segments (OS). In rod-specific knockouts (rodCep164-/-), Cre expression starts after P9 and CC/OS form. P16 rodCep164-/- rods have nearly normal OS lengths, and maintain OS attachment through P21 despite loss of CEP164. Intraflagellar transport components (IFT88, IFT57 and IFT140) were reduced at P16 rodCep164-/- BBs and CC tips and nearly absent at P21, indicating impaired intraflagellar transport. Nascent OS discs, labeled with a fluorescent dye on P14 and P18 and harvested on P19, showed continued rodCep164-/- disc morphogenesis but absence of P14 discs mid-distally, indicating OS instability. Tamoxifen induction with PROM1ETCre;Cep164F/F (tamCep164-/-) adult mice affected maintenance of both rod and cone OS. The results suggest that CEP164 is key towards recruitment and stabilization of IFT-B particles at BB/CC. Impairment of IFT may be the main driver of ciliary malfunction observed with hypomorphic CEP164 mutations. Author summaryCentrosomal protein of 164 kDa (CEP164) is indispensable for docking of basal bodies to apical membranes and formation of primary cilia. Homozygous truncations of CEP164 are associated with severe ciliopathy whereas missense mutations generate milder forms of NPHP. Recessive mutations of CEP164 are associated with nephronophthisis (NPHP), Meckel-Gruber (MKS) and Bardet-Biedl syndromes (BBS) in which primary cilia fail to form, or do not function correctly. We found that deletion of CEP164 in mouse photoreceptors before docking of the basal body (BB) to the apical inner segment membrane prevents elaboration of connecting cilia (CC, equivalent to transition zones) and outer segments (OSs, modified primary cilia). We also generated mouse models in which deletion of CEP164 occurs after OS are established and observed that the BB/CC and axoneme are initially stable in the absence of CEP164. Loss of CEP164, however, diminished recruitment of IFT-B proteins to the BB/CC affecting intraflagellar transport (IFT), which is required for maintenance of cilia and OSs. We propose that, in ciliopathies caused by missense mutations (e.g., X1460WextX57 associated with LCA) impairment of IFT provides a mechanism for ciliary dysfunction and disease.

neuroscience↗

bioRxiv2020

Deletion of INPP5E in the murine retina impairs axoneme formation and prevents photoreceptor disc morphogenesis

INPP5E (pharbin) is a ubiquitously-expressed, farnesylated phosphatidylinositol polyphosphate 5-phosphatase which modulates the phosphoinositide composition of membranes. INPP5E resides in primary cilia, and mutations or loss of INPP5E are associated with ciliary dysfunction. INPP5E missense mutations of the phosphatase catalytic domain cause Joubert syndrome in humans, a syndromic ciliopathy affecting multiple tissues including brain, liver, kidney and retina. We show that, differing from other primary cilia, INPP5E is present in the wildtype photoreceptor inner segment and absent in the outer segment--a modified primary cilium dedicated to phototransduction. We generated Inpp5eF/F;Six3Cre (in short, retInpp5e-/-) mice which exhibit a rapidly progressing rod-cone degeneration nearly completed by postnatal day 21 (P21) in the central retina. Mutant cone outer segments contain vesicles instead of discs as early as P8. While P10 mutant outer segments contain phototransduction and structural proteins, they do not form axonemes and fail to elaborate disc membranes. Connecting cilia of retInpp5e-/- rods appear normal, although IFT-B/A particles accumulate at their distal ends suggesting disrupted intraflagellar transport. These results show that ablation of INPP5E does not impair the secretory pathway responsible for delivery of outer segment-specific proteins, but blocks axonemal extension and prevents disc morphogenesis.

neuroscience↗

bioRxiv2018

Electron transfer dictates metabolic reprogramming in proliferating cells under hypoxia

Metabolic reprogramming extensively occurs in proliferating cancer cells. This phenomenon occurs highly heterogeneously, but its origin has remained unclear. Here we use a physicochemical concept of free electron potential (FEP) and its equation of state to profile metabolites. We demonstrate that FEP change between substrates and products exactly reflects electrons dissipated in a metabolic transformation. Based on the law of conservation of electron in chemical reactions, a function of FEP change for central metabolism in proliferating cells are further derived, and it can accurately predict metabolic behaviors under hypoxia by maximizing the cellular FEP change to consume electrons. Therefore, enabling electron transfer dictates metabolic reprogramming in hypoxic cells, which underlies the major findings in cancer metabolism and is supported by our experiments. Importantly, our model established on FEP helps to reveal a combination of promising targets to inhibit tumor growth under hypoxia by blocking electron consumption, and could also guide future studies on cancer metabolism under hypoxia.

biochemistry↗