Glycerol kinase-like proteins cooperate with Pld6 in regulating sperm mitochondrial sheath formation and male fertility

Chen, Yuxi; Liang, Puping; Huang, Yan; Li, Minyan; Zhang, Xiya; Ding, Chenhui; Feng, Jiayi; Zhang, Zhen; Zhang, Xueqing; Gao, Yuanzhu; Zhang, Qinfeng; Cao, Sheng‐Li; Zheng, Haiyan; Liú, Dan; Songyang, Zhou; Huang, Junjiu

doi:10.1038/celldisc.2017.30

Cited by 32 publications

(33 citation statements)

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“…The enzymatic function of PLD 3 , PLD 4 and PLD 5 remains unknown (the first two are ER type 2 transmembrane proteins that have two HKD motifs but lack both the PX and PH domains) (Nelson and Frohman, ). PLD 6 localizes to the outer mitochondrial membrane where it acts as a cardiolipin hydrolase to generate PA (Chen et al, ). In mammals, PLD is a key enzyme in cell signalling, the function of which is mainly attributed to its reaction product, PA, and other converted lipid mediators.…”

Section: Phospholipasesmentioning

confidence: 99%

Phospholipases in neuronal function: A role in learning and memory?

Joensuu

Wallis

Saber

et al. 2020

Journal of Neurochemistry

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| LIPIDS AND THE B R AINUnderstanding how the over 80 billion neurons in the human brain communicate with each other to generate a self-aware mind remains one of the great challenges of modern neurobiology. Despite decades of ever more sophisticated study and progress, the molecular mechanisms underpinning the exquisitely regulated neuronal communication at the heart of cognition, learning and memory remain incompletely understood. The discovery that neurotransmission is quantal (Del Castillo and Katz, 1954) led to the development of the vesicle hypothesis in which neurotransmitters are released following fusion of synaptic vesicles with the pre-synaptic membrane in a process known as neuroexocytosis. Decades of subsequent research validated this fundamental finding, and demonstrated the involvement of sophisticated protein machinery (e.g. SNAREs, N-ethylmaleimide-sensitive factor attachment receptors) in all aspects of vesicle trafficking. Most recently, the analysis of brain lipids and lipid metabolites has started to shift this somewhat 'proteocentric' view of neurotransmission to a more holistic view involving tightly regulated protein-protein, protein-lipid (Wenk and De Camilli, 2004) and lipid-lipid interactions, all of which are essential for neuronal communication.Indeed, the healthy human brain is composed of approximately 60% lipid by dry weight, higher than in any other tissue. Seminal chromatography experiments (O'Brien and Sampson, 1965) AbstractDespite the human brain being made of nearly 60% fat, the vast majority of studies on the mechanisms of neuronal communication which underpin cognition, memory and learning, primarily focus on proteins and/or (epi)genetic mechanisms. Phospholipids are the main component of all cellular membranes and function as substrates for numerous phospholipid-modifying enzymes, including phospholipases, which release free fatty acids (FFAs) and other lipid metabolites that can alter the intrinsic properties of the membranes, recruit and activate critical proteins, and act as lipid signalling molecules. Here, we will review brain specific phospholipases, their roles in membrane remodelling, neuronal function, learning and memory, as well as their disease implications. In particular, we will highlight key roles of unsaturated FFAs, particularly arachidonic acid, in neurotransmitter release, neuroinflammation and memory.In light of recent findings, we will also discuss the emerging role of phospholipase A 1 and the creation of saturated FFAs in the brain. K E Y W O R D S exocytosis, free fatty acids, learning, memory, phospholipases, phospholipids, synaptic plasticity | 301 JOENSUU Et al.

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Section: Phospholipasesmentioning

confidence: 99%

Phospholipases in neuronal function: A role in learning and memory?

Joensuu

Wallis

Saber

et al. 2020

Journal of Neurochemistry

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“…In our opinion, an increased carbonylation of the kinases and phosphatases, PKA, PP-1γ, and GK2, observed in LQ ejaculates, may lead to abnormal phosphorylation/dephosphorylation of sperm proteins. GK2 and PP-1γ are key proteins involved in energetic metabolism and the regulation of sperm motility [ 35 , 36 ]. However, among the identified proteins, PKA is the major player responsible for the activation of sperm tyrosine kinases (with serine and threonine residues) to trigger a cascade of protein phosphorylation involved in sperm motility and capacitation.…”

Section: Discussionmentioning

confidence: 99%

“…UCRI and ATP 5B are involved in electron transfer and proton gradient formation, respectively. In turn, PKA, GK2, and PP-1γ are testis-specific isoforms of enzymes involved in sperm motility and flagella development [ 35 , 36 , 40 ]. Moreover, ODF 2 is a component of the outer dense fibres of the main cytoskeletal structure of the sperm tail, and carbonylation of this protein was also observed in our previous study in cryopreserved bull semen [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, ODF 2 is a component of the outer dense fibres of the main cytoskeletal structure of the sperm tail, and carbonylation of this protein was also observed in our previous study in cryopreserved bull semen [ 23 ]. Oxidative damage of the above proteins can lead to inefficient ATP production and impaired mitochondrial function and flagella morphology [ 35 , 41 ]. In conclusion, our results suggest that the production of LQ ejaculates is associated with elevated ROS levels, which cause the increased carbonylation of mitochondrial and mitochondria-adjacent cytoskeletal proteins, and eventually may affect mitochondrial and flagella function, which may explain the poor motility of sperm in LQ ejaculates.…”

Section: Discussionmentioning

confidence: 99%

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Differences in sperm protein abundance and carbonylation level in bull ejaculates of low and high quality

et al. 2018

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In breeding and insemination centres, significant variation in bull ejaculate quality is often observed between individuals and also within the same individual. Low-quality semen does not qualify for cryopreservation and is rejected, generating economic loss. The mechanisms underlying the formation of low-quality ejaculates are poorly understood; therefore, the aim of the present study was to investigate the proteomic differences and oxidative modifications (measured as changes in protein carbonylation level) of bull ejaculates of low and high quality. Flow cytometry and computer-assisted sperm analysis were used to assess differences in viability, reactive oxygen species (ROS) level, and sperm motility. To analyse changes in protein abundance, two-dimensional difference gel electrophoresis (2D-DIGE) was performed. Western blotting in conjunction with two-dimensional electrophoresis (2D-oxyblot) was used to quantitate carbonylated sperm proteins. Proteins were identified using matrix-assisted laser desorption/ionisation time-of-flight/time-of-flight spectrometry. High quality ejaculates were characterised by higher sperm motility, viability, concentration, and a lower number of ROS-positive cells (ROS+). We found significant differences in the protein profile between high- and low-quality ejaculates, and identified 14 protein spots corresponding to 10 proteins with differences in abundance. The identified sperm proteins were mainly associated with energetic metabolism, capacitation, fertilisation, motility, and cellular detoxification. High-quality ejaculates were characterised by a high abundance of extracellular sperm surface proteins, likely due to more efficient secretion from accessory sex glands and/or epididymis, and a low abundance of intracellular proteins. Our results show that sperm proteins in low-quality ejaculates are characterised by a high carbonylation level. Moreover, we identified, for the first time, 14 protein spots corresponding to 12 proteins with differences in carbonylation level between low- and high-quality ejaculates. The carbonylated proteins were localised mainly in mitochondria or their immediate surroundings. Oxidative damage to proteins in low-quality semen may be associated with phosphorylation/dephosphorylation disturbances, mitochondrial dysfunction, and motility apparatus disorders. Our results contribute to research regarding the mechanism by which low- and high-quality ejaculates are formed and to the identification of sperm proteins that are particularly sensitive to oxidative damage.

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“…10: 200186 configurations. For instance, conventional EM demonstrated that mammalian sperm mitochondria are arranged in a tight spiral around the flagellar axoneme [39][40][41], and that the mammalian sperm axoneme is surrounded by a plethora of accessory structures that dwarf the axoneme proper [13] (figure 1b). These characteristics are general features of mammalian sperm, but details such as the number of mitochondria in the midpiece and the sizes of the accessory elements vary across species (reviewed in [12,13]).…”

Section: Conventional Em Has Contributed Greatly To Our Understandingmentioning

confidence: 99%

Looking back and looking forward: contributions of electron microscopy to the structural cell biology of gametes and fertilization

2020

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Mammalian gametes—the sperm and the egg—represent opposite extremes of cellular organization and scale. Studying the ultrastructure of gametes is crucial to understanding their interactions, and how to manipulate them in order to either encourage or prevent their union. Here, we survey the prominent electron microscopy (EM) techniques, with an emphasis on considerations for applying them to study mammalian gametes. We review how conventional EM has provided significant insight into gamete ultrastructure, but also how the harsh sample preparation methods required preclude understanding at a truly molecular level. We present recent advancements in cryo-electron tomography that provide an opportunity to image cells in a near-native state and at unprecedented levels of detail. New and emerging cellular EM techniques are poised to rekindle exploration of fundamental questions in mammalian reproduction, especially phenomena that involve complex membrane remodelling and protein reorganization. These methods will also allow novel lines of enquiry into problems of practical significance, such as investigating unexplained causes of human infertility and improving assisted reproductive technologies for biodiversity conservation.

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Glycerol kinase-like proteins cooperate with Pld6 in regulating sperm mitochondrial sheath formation and male fertility

Cited by 32 publications

References 54 publications

Phospholipases in neuronal function: A role in learning and memory?

Phospholipases in neuronal function: A role in learning and memory?

Differences in sperm protein abundance and carbonylation level in bull ejaculates of low and high quality

Looking back and looking forward: contributions of electron microscopy to the structural cell biology of gametes and fertilization

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