Lack of the nucleoside transporter ENT1 results in the Augustine-null blood type and ectopic mineralization

Daniels, Geoff; Ballif, Bryan A.; Helias, Virginie; Saison, Carole; Grimsley, Shane; Mannessier, L.; Hustinx, Hein; Lee, Edmond; Cartron, Jean‐Pierre; Peyrard, Thierry; Arnaud, Lionel

doi:10.1182/blood-2015-03-631598

Cited by 47 publications

(78 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Indeed ENT1 may affect these neurological conditions, which is particularly interesting given the newly established role of ENT1 and purinergic signaling in musculoskeletal function as well as the association of ENT1 dysfunction with neurological abnormalities. 47–49 …”

Section: Discussionmentioning

confidence: 99%

Label-Free Neuroproteomics of the Hippocampal-Accumbal Circuit Reveals Deficits in Neurotransmitter and Neuropeptide Signaling in Mice Lacking Ethanol-Sensitive Adenosine Transporter

et al. 2017

View full text Add to dashboard Cite

The neural circuit of the dorsal hippocampus (dHip) and nucleus accumbens (NAc) contributes to cue-induced learning and addictive behaviors, as demonstrated by the escalation of ethanol-seeking behaviors observed following deletion of the adenosine equilibrative nucleoside transporter 1 (ENT1−/−) in mice. Here we perform quantitative LC–MS/ MS neuroproteomics in the dHip and NAc of ENT1−/− mice. Using Ingenuity Pathway Analysis, we identified proteins associated with increased long-term potentiation, ARP2/3-mediated actin cytoskeleton signaling and protein expression patterns suggesting deficits in glutamate degradation, GABAergic signaling, as well as significant changes in bioenergetics and energy homeostasis (oxidative phosphorylation, TCA cycle, and glycolysis). These pathways are consistent with previously reported behavioral and biochemical phenotypes that typify mice lacking ENT1. Moreover, we validated decreased expression of the SNARE complex protein VAMP1 (synaptobrevin-1) in the dHip as well as decreased expression of pro-dynorphin (PDYN), neuroendocrine convertase (PCSK1), and Leu-Enkephalin (dynorphin-A) in the NAc. Taken together, our proteomic approach provides novel pathways indicating that ENT1-regulated signaling is essential for neurotransmitter release and neuropeptide processing, both of which underlie learning and reward-seeking behaviors.

show abstract

Section: Discussionmentioning

confidence: 99%

Label-Free Neuroproteomics of the Hippocampal-Accumbal Circuit Reveals Deficits in Neurotransmitter and Neuropeptide Signaling in Mice Lacking Ethanol-Sensitive Adenosine Transporter

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Consequently, osteoblast marker gene expression and osteoblast differentiation increases in ENT1 null mice [42, 57]. However, ENT1-null mice manifest an osteopenic phenotype with increased bone turnover [57–59] perhaps due to a dominant effect of ENT1 on osteoclast formation than osteoblast differentiation [57]. Mirroring these effects, loss of function ENT1 mutations also impairs bone homeostasis in humans [59].…”

Section: Influence Of Adipocyte-secreted Signaling Molecules On Bone mentioning

confidence: 99%

“…However, ENT1-null mice manifest an osteopenic phenotype with increased bone turnover [57–59] perhaps due to a dominant effect of ENT1 on osteoclast formation than osteoblast differentiation [57]. Mirroring these effects, loss of function ENT1 mutations also impairs bone homeostasis in humans [59]. Conversely, mutations in an acidic pH-dependent lysosomal adenosine transporter ENT3 [60] result in reduced resorptive abilities of osteoclasts leading to dysosteosclerosis, a form of osteopetrosis in humans [61].…”

Section: Influence Of Adipocyte-secreted Signaling Molecules On Bone mentioning

confidence: 99%

Bone Marrow Adipose Tissue and Skeletal Health

Muruganandan

Govindarajan

Sinal

2018

Curr Osteoporos Rep

View full text Add to dashboard Cite

Purpose of Review To summarize and discuss recent progress and novel signaling mechanisms relevant to bone marrow adipocyte formation and its physiological/pathophysiological implications for bone remodeling. Recent Findings Skeletal remodeling is a coordinated process entailing removal of old bone and formation of new bone. Several bone loss disorders such as osteoporosis are commonly associated with increased bone marrow adipose tissue. Experimental and clinical evidence supports that a reduction in osteoblastogenesis from mesenchymal stem cells at the expense of adipogenesis, as well as the deleterious effects of adipocyte-derived signaling, contributes to the etiology of osteoporosis as well as bone loss associated with aging, diabetes mellitus, post-menopause, and chronic drug therapy. However, this view is challenged by findings indicating that, in some contexts, bone marrow adipose tissue may have a beneficial impact on skeletal health. Summary Further research is needed to better define the role of marrow adipocytes in bone physiology/pathophysiology and to determine the therapeutic potential of manipulating mesenchymal stem cell differentiation.

show abstract

“…Interestingly, these mice show evidence of ectopic bone mineralization with involvement of the spine and sternal fibrocartilaginous tissue, a condition which is similar to lesions seen in diffuse idiopathic skeletal hyperostosis (DISH) [39,40]. Similarly, individuals lacking ENT1 (homozygous for a null mutation in SLC29A1) suffer from ectopic mineralization suggesting the role of ENT1 in bone metabolism in vivo [41]. In 2014, Hinton et al investigated the bone characteristics in ENT1 null mice and observed abnormal changes including decreased bone density in the lower half of the spinal cord and femur, increased markers of osteoclast activity in the femur, and increased bone density in the cervical and upper thoracic vertebrae [42].…”

Section: Adenosine Signalingmentioning

confidence: 88%

Regulation of bone and cartilage by adenosine signaling

Strazzulla

Cronstein

2016

Purinergic Signalling

View full text Add to dashboard Cite

There is growing recognition that bone serves important endocrine and immunologic functions that are compromised in several disease states. While many factors are known to affect bone metabolism, recent attention has focused on investigating the role of purinergic signaling in bone formation and regulation. Adenosine is a purine nucleoside produced intracellularly and extracellularly in response to stimuli such as hypoxia and inflammation, which then interacts with P1 receptors. Numerous studies have suggested that these receptors play a pivotal role in osteoblast, osteoclast, and chondrocyte differentiation and function. This review discusses the various ways by which adenosine signaling contributes to bone and cartilage homeostasis, while incorporating potential therapeutic applications of these signaling pathways.

show abstract

Lack of the nucleoside transporter ENT1 results in the Augustine-null blood type and ectopic mineralization

Abstract: Key Points SLC29A1 encoding the equilibrative nucleoside transporter 1 (ENT1) specifies a novel blood group system that includes the Ata antigen. Although At(a−) people of African ancestry have functional ENT1, 3 siblings of European ancestry were identified who do not express ENT1.

Cited by 47 publications

References 19 publications

Label-Free Neuroproteomics of the Hippocampal-Accumbal Circuit Reveals Deficits in Neurotransmitter and Neuropeptide Signaling in Mice Lacking Ethanol-Sensitive Adenosine Transporter

Label-Free Neuroproteomics of the Hippocampal-Accumbal Circuit Reveals Deficits in Neurotransmitter and Neuropeptide Signaling in Mice Lacking Ethanol-Sensitive Adenosine Transporter

Bone Marrow Adipose Tissue and Skeletal Health

Regulation of bone and cartilage by adenosine signaling

Contact Info

Product

Resources

About