Less is more： Nutrient limitation induces cross-talk of nutrient sensing pathways with NAD~ homeostasis and contributes to longevity

Nutrient sensing pathways and their regulation grant cells control over their metabolism and growth in response to changing nutrients. Factors that regulate nutrient sensing can also modulate longevity. Reduced activity of nutrient sensing pathways such as glucose-sensing PKA, nitrogen-sensing TOR and S6 kinase homolog Sch9 have been linked to increased life span in the yeast, Saccharomyces cerevisiae, and higher eukaryotes. Recently, reduced activity of amino acid sensing SPS pathway was also shown to increase yeast life span. Life span extension by reduced SPS activity requires enhanced NAD＋ （nicotinamide adenine dinucleotide, oxidized form） and nicotinamide riboside （NR, a NAD＋ precursor） homeostasis. Maintaining adequate NAD＋ pools has been shown to play key roles in life span extension, but factors regulating NAD＋ metabolism and homeostasis are not completely understood. Recently, NAD＋ metabolism was also linked to the phosphate （Pi）-sensing PHO pathway in yeast. Canonical PHO activation requires Pi-starvation. Interestingly, NAD＋ depletion without Pi-starvation was sufficient to induce PHO activation, increasing NR production and mobilization. Moreover, SPS signaling appears to function in parallel with PHO signaling components to regulate NR/NAD＋ homeostasis. These studies suggest that NAD＋ metabolism is likely controlled by and/or coordinated with multiple nutrient sensing pathways. Indeed, cross-regulation of PHO, PKA, TOR and Sch9 pathways was reported to potentially affect NAD＋ metabolism; though detailed mechanisms remain unclear. This review discusses yeast longevity- related nutrient sensing pathways and possible mechanisms of life span extension, regulation of NAD＋ homeostasis, and cross-talk among nutrient sensing pathways and NAD＋ homeostasis.

Plant mineral nutrient sensing and signaling

As terrestrial plants are sessile organisms and therefore must directly deal with an often complex and changing environment, they have had to develop complex and elegant strategies to survive and thrive in the face of environmental stress. This is particularly true for plant adaptation to the soil environment, where essential mineral nutrients often are found at sub- optimal levels and their concentrations can vary significantly, both spatially and temporally. Furthermore, plants also at times have to respond to excessively high and potentially toxic levels of essential nutrients, as well as toxic levels of non- essential metals and metalloids in the soil. Although plant mineral nutrition as a bona ~ide research discipline has a history of over 15o years, beginning with the pioneering work of Justus Von Liebieg and others in the mid-1800＇s, it is only very recently that researchers have begun to truly appreciate how sophisticated plants are with regards to the sensing of their mineral status and the maintaining of mineral homeostasis in the plant.

Metabolic and proteostatic differences in quiescent and active neural stem cells

Adult neural stem cells are neurogenesis progenitor cells that play an important role in neurogenesis.Therefore,neural regeneration may be a promising target for treatment of many neurological illnesses.The regenerative capacity of adult neural stem cells can be chara cterized by two states:quiescent and active.Quiescent adult neural stem cells are more stable and guarantee the quantity and quality of the adult neural stem cell pool.Active adult neural stem cells are chara cterized by rapid proliferation and differentiation into neurons which allow for integration into neural circuits.This review focuses on diffe rences between quiescent and active adult neural stem cells in nutrition metabolism and protein homeostasis.Furthermore,we discuss the physiological significance and underlying advantages of these diffe rences.Due to the limited number of adult neural stem cells studies,we refe rred to studies of embryonic adult neural stem cells or non-mammalian adult neural stem cells to evaluate specific mechanisms.

开展陆生与水产养殖动物营养感知研究的展望

饲料在动物生长和健康中扮演着重要的角色,然而决定饲料表现的内在机一直是一个所谓的“黑箱”。直到近年来,研究证明营养素能够作为信号分子被细胞和机体感知,并在调控基因表达和代谢活动中起着至关重要的作用。多条分别感知不同营养素的信号通路被发现,营养感知信号调节也已在临床医学中被广泛用于药物开发与疾病控制。然而,在陆生和水产养殖动物中,对主要营养素(蛋白质、糖脂等)的营养感知和代谢调控的研究仍处于起步阶段。因此,我们针对未来在动物营养学中开展营养感知研究可能的研究主题和应用场景提出设想和建议。

A transceptor-channel complex couples nitrate sensing to calcium signaling in Ambidopsis

Nitrate-induced Ca^(2+) signaling is crucial for the primary nitrate response in plants.However,the molecular mechanism underlying the generation of the nitrate-specific calcium signature remains unknown.We report here that a cyclic nucleotide-gated channel(CNGC)protein,CNGC15,and the nitrate transceptor(NRT1.1)constitute a molecular switch that controls calcium influx depending on nitrate levels.The expression of CNGC15 is induced by nitrate,and its protein is localized at the plasma membrane after establishment of young seedlings.We found that disruption of CNGC15 results in the loss of the nitrate-induced Ca^(2+) signature(primary nitrate response)and retards root growth,reminiscent of the phenotype observed in the nrt1.1 mutant.We further showed that CNGC15 is an active Ca^(2+)-permeable channel that physically interacts with the NRT1.1 protein in the plasma membrane.Importantly,we discovered that CNGC15-NRT1.1 interaction silences the channel activity of the heterocomplex,which dissociates upon a rise in nitrate levels,leading to reactivation of the CNGC15 channel.The dynamic interactions between CNGC15 and NRT1.1 therefore control the channel activity and Ca^(2+) influx in a nitrate-dependent manner.Our study reveals a new nutrient-sensing mechanism that utilizes a nutrient transceptor-channel complex assembly to couple nutrient status to a specific Ca^(2+) signature.

Nutrient-hormone relations:Driving root plasticity in plants

Optimal plant development requires root uptake of 14 essential mineral elements from the soil.Since the bioavailability of these nutrients underlies large variation in space and time,plants must dynamically adjust their root architecture to optimize nutrient access and acquisition.The information on external nutrient availability and whole-plant demand is translated into cellular signals that often involve phytohormones as intermediates to trigger a systemic or locally restricted developmental response.Timing and extent of such local root responses depend on the overall nutritional status of the plant that is transmitted from shoots to roots in the form of phytohormones or other systemic long-distance signals.The integration of these systemic and local signals then determines cell division or elongation rates in primary and lateral roots,the initiation,emergence,or elongation of lateral roots,as well as the formation of root hairs.Here,we review the cascades of nutrient-related sensing and signaling events that involve hormones and highlight nutrient-hormone relations that coordinate root developmental plasticity in plants.

The SWI/SNF chromatin-remodeling factors BAF60a, b, and c in nutrient signaling and metabolic control

Metabolic syndrome has become a global epidemic that adversely affects human health. Both genetic and environmental factors contribute to the pathogenesis of metabolic disorders; however, the mechanisms that integrate these cues to regulate metabolic physiology and the development of metabolic disorders remain incompletely defined. Emerging evidence suggests that SWlISNF chromatin.remodeling complexes are critical for directing metabolic reprogramming and adaptation in response to nutritional and other physiological sigrials. The ATP-dependent SWl/SNF ing complexes comprise up to 11 subunits, among which the BAF60 subunit serves as a key link between the core complexes and specific transcriptional factors. The BAF60 subunit has three members, BAF60a, b, and c. The distinct tissue distribution patterns and regulatory mechanisms of BAF60 proteins confer each isoform with specialized functions in different m^abolic cell types. In this review, we summarize the emerging roles and mechanisms of BAF60 proteins in the regulation of nutrient sensing and energy metabolism under physiological and disease conditions.

Sailing in complex nutrient signaling networks:Where I am,where to go,and how to go?

To ensure survival and promote growth,sessile plants have developed intricate internal signaling networks tailored in diverse cells and organs with both shared and specialized functions that respond to various internal and external cues.A fascinating question arises:how can a plant cell or organ diagnose the spatial and temporal information it is experiencing to know“where I am,”and then is able to make the accurate specific responses to decide“where to go”and“how to go,”despite the absence of neuronal systems found in mammals.Drawing inspiration from recent comprehensive investigations into diverse nutrient signaling pathways in plants,this review focuses on the interactive nutrient signaling networks mediated by various nutrient sensors and transducers.We assess and illustrate examples of how cells and organs exhibit specific responses to changing spatial and temporal information within these interactive plant nutrient networks.In addition,we elucidate the underlying mechanisms by which plants employ posttranslational modification codes to integrate different upstream nutrient signals,thereby conferring response specificities to the signaling hub proteins.Furthermore,we discuss recent breakthrough studies that demonstrate the potential of modulating nutrient sensing and signaling as promising strategies to enhance crop yield,even with reduced fertilizer application.

Exploring the potential for an evolutionarily conserved role of the taste 1 receptor gene family in gut sensing mechanisms of fish

In this study,we investigated the transcriptional spatio-temporal dynamics of the taste 1 receptor(T1R)gene family repertoire in seabream(Sparus aurata[sa]),during larval ontogeny and in adult tissues.In early larval development,sa T1R expression arises heterochronously,i.e.the extraoral taste-related perception in the gastrointestinal tract(GIT)anticipates first exogenous feeding(at 9 days post hatching[dph]),followed by the buccal/intraoral perception from 14 dph onwards,supporting the hypothesis that the early onset of the molecular machinery underlying sa T1R expression in the GIT is not induced by food but rather genetically hardwired.During adulthood,we characterized the expression patterns of sa T1R within specific tissues(n=4)distributed in oropharingeal,GIT and brain regions substantiating their functional versatility as chemosensory signaling players to a variety of biological functions beyond oral taste sensation.Further,we provided for the first time direct evidences in fish for m RNA coexpression of a subset of sa T1R genes(mostly sa T1R3,i.e.the common subunit of the heterodimeric T1R complexes for the detection of“sweet”and“umami”substances),with the selected gut peptides ghrelin(ghr),cholecystokinin(cck),hormone peptide yy(pyy)and proglucagon(pg).Each peptide defines the enteroendocrine cells(ECCs)identity,and establishes on morphological basis,a direct link for T1R chemosensing in the regulation of fish digestive processes.Finally,we analyzed the spatial gene expression patterns of 2 taste signaling components functionally homologous to the mammalian G(i)a subunit gustducin,namely sa G(i)a1 and sa G(i)a2,and demonstrated their co-localization with the sa T1R3in EECs,thus validating their direct involvement in taste-like transduction mechanisms of the fish GIT.In conclusion,data provide new insights in the evolutionary conservation of gut sensing in fish suggesting a conserved role for nutrient sensors modulating entero-endocrine secretion.

The Arabidopsis AP2/ERF Transcription Factor RAP2.11 Modulates Plant Response to Low-Potassium Conditions

Plants respond to low-nutrient conditions through metabolic and morphology changes that increase their ability to survive and grow. The transcription factor RAP2.11 was identified as a component in the response to low potassium through regulation of the high-affinity K＋ uptake transporter AtHAK5 and other components of the low- potassium signal transduction pathway. RAP2.11 was identified through the activation tagging of Arabidopsis lines that contained a luciferase marker driven by the AtHAK5 promoter that is normally only induced by low potassium. This factor bound to a GCC-box of the AtHAK5 promoter in vitro and in vivo. Transcript profiling revealed that a large number of genes were up-regulated in roots by RAP2.11 overexpression. Many regulated genes were identified to be in functional cate- gories that are important in Iow-K＋ signaling. These categories included ethylene signaling, reactive oxygen species pro- duction, and calcium signaling. Promoter regions of the up-regulated genes were enriched in the GCCGGC motif also contained in the AtHAK5 promoter. These results suggest that RAP2.11 regulates AtHAK5 expression under Iow-K＋ con- ditions and also contributes to a coordinated response to low-potassium conditions through the regulation of other genes in the Iow-K＋ signaling cascade.

Plant target of rapamycin signaling network:Complexes,conservations,and specificities

Target of rapamycin(TOR)is an evolutionarily conserved protein kinase that functions as a central signaling hub to integrate diverse internal and external cues to precisely orchestrate cellular and organismal physiology.During evolution,TOR both maintains the highly conserved TOR complex compositions,and cellular and molecular functions,but also evolves distinctive roles and strategies to modulate cell growth,proliferation,metabolism,survival,and stress responses in eukaryotes.Here,we review recent discoveries on the plant TOR signaling network.We present an overview of plant TOR complexes,analyze the signaling landscape of the plant TOR signaling network from the upstream signals that regulate plant TOR activation to the downstream effectors involved in various biological processes,and compare their conservation and specificities within different biological contexts.Finally,we summarize the impact of dysregulation of TOR signaling on every stage of plant growth and development,from embryogenesis and seedling growth,to flowering and senescence.

Signal integration in the （m）TORC1 growth pathway

BACKGROUND： The protein kinase Target Of Rapamycin （TOR） is a nexus for the regulation of eukaryotic cell growth. TOR assembles into one of two distinct signalling complexes, TOR complex 1 （TORC1） and TORC2 （mTORC1/2 in mammals）, with a set of largely non-overlapping protein partners. （m）TORC 1 activation occurs in response to a series of stimuli relevant to cell growth, including nutrient availability, growth factor signals and stress, and regulates much of the cell＇s biosynthetic activity, from proteins to lipids, and recycling through autophagy, mTORC1 regulation is of great therapeutic significance, since in humans many of these signalling complexes, alongside subunits of mTORC1 itself, are implicated in a wide variety of pathophysiologies, including multiple types of cancer, neurological disorders, neurodegenerative diseases and metabolic disorders including diabetes. METHODOLOGY： Recent years have seen numerous structures determined of （m）TOR, which have provided mechanistic insight into （m）TORC 1 activation in particular, however the integration of cellular signals occurs upstream of the kinase and remains incompletely understood. Here we have collected and analysed in detail as many as possible of the molecular and structural studies which have shed light on （m）TORC 1 repression, activation and signal integration. CONCLUSIONS： A molecular understanding of this signal integration pathway is required to understand how （m）TORC1 activation is reconciled with the many diverse and contradictory stimuli affecting cell growth. We discuss the current level of molecular understanding of the upstream components of the （m）TORC1 signalling pathway, recent progress on this key biochemical frontier, and the future studies necessary to establish a mechanistic understanding of this master-switch for eukaryotic cell growth.

Membrane-bound O-acyltransferases(MBOATs)

The MBOATenzyme family,identified in 2000,comprises 11 genes in the human genome that participate in a variety of biological processes.MBOAT enzymes contain multiple transmembrane domains and share two active site residues,histidine and asparagine.Several MBOAT members are drug targets for major human diseases,including atherosclerosis,obesity,Alzheimer disease,and viral infections.Here we review the historical aspects of MBOAT enzymes,classify them biochemically into 3 subgroups,and describe the essential features of each member.