Mouse spermatogenic cell-specific type 1 hexokinase (mHk1-s) transcripts are expressed by alternative splicing from themHk1 gene and the HK1-S protein is localized mainly in the sperm tail

Mori, Chisato; Nakamura, Noriko; Welch, Janet L.; Gotoh, Hiroki; Goulding, Eugenia H.; Fujioka, Makio; Eddy, E. M.

doi:10.1002/(sici)1098-2795(199804)49:4<374::aid-mrd4>3.0.co;2-k

Cited by 102 publications

(69 citation statements)

References 42 publications

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“…35 Relatively little is known about the functions of non-bound HK1. PBD-lacking transcripts are expressed in mouse spermatogenic cells, with alternative splicing of the upstream exons subject to developmental regulation, 15,18 similar to our observations on AltT2-containing transcripts in the peripheral nerve. The translated protein is localised in the sperm tail and not with the mitochondria.…”

Section: Discussionsupporting

confidence: 86%

“…The translated protein is localised in the sperm tail and not with the mitochondria. 15 In the brain axons, HK1 was shown to be transported independent of the mitochondria and to associate with presynaptic terminals. 36 Microarray analysis of the peripheral nerve has shown that HK1 is developmentally regulated with the highest expression observed prenatally; 37 however, the data do not allow any conclusions on the differential expression of isoforms.…”

Section: Discussionmentioning

confidence: 99%

“…We characterised AltT2-containing transcripts in mouse newborn and adult neural tissues in comparison with the testis, which is particularly enriched in alternative splicing, 21 and where the HK1 5 0 upstream region has been studied in detail. 13,15,18 RT-PCR with different combinations of primers in exons T1 and AltT2 (forward), and T3 and ubiquitous 2 (reverse) revealed a total of 13 alternative transcripts. In both the testis and neural cells, the overall level of AltT2-containing transcripts was markedly lower than the invariable coding region of HK1 (not shown).…”

Section: Genetic Analysesmentioning

confidence: 99%

“…The C-terminus is conserved between the different isozymes and involved in the catalytic activity, while evolutionary divergence of the N-terminal half is thought to be related to regulatory functions. 14,15 HK1 is ubiquitously expressed and particularly abundant in the brain, the testis and erythrocytes. It contains 18 translated exons, with the last 17 present in all known transcripts.…”

Section: Genetic Analysesmentioning

confidence: 99%

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A mutation in an alternative untranslated exon of hexokinase 1 associated with Hereditary Motor and Sensory Neuropathy – Russe (HMSNR)

et al. 2009

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Hereditary Motor and Sensory Neuropathy -Russe (HMSNR) is a severe autosomal recessive disorder, identified in the Gypsy population. Our previous studies mapped the gene to 10q22-q23 and refined the gene region to B70 kb. Here we report the comprehensive sequencing analysis and fine mapping of this region, reducing it to B26 kb of fully characterised sequence spanning the upstream exons of Hexokinase 1 (HK1). We identified two sequence variants in complete linkage disequilibrium, a G4C in a novel alternative untranslated exon (AltT2) and a G4A in the adjacent intron, segregating with the disease in affected families and present in the heterozygote state in only 5/790 population controls. Sequence conservation of the AltT2 exon in 16 species with invariable preservation of the G allele at the mutated site, strongly favour the exonic change as the pathogenic mutation. Analysis of the Hk1 upstream region in mouse mRNA from testis and neural tissues showed an abundance of AltT2-containing transcripts generated by extensive, developmentally regulated alternative splicing. Expression is very low compared with ubiquitous Hk1 and all transcripts skip exon1, which encodes the protein domain responsible for binding to the outer mitochondrial membrane, and regulation of energy production and apoptosis. Hexokinase activity measurement and immunohistochemistry of the peripheral nerve showed no difference between patients and controls. The mutational mechanism and functional effects remain unknown and could involve disrupted translational regulation leading to increased anti-apoptotic activity (suggested by the profuse regenerative activity in affected nerves), or impairment of an unknown HK1 function in the peripheral nervous system (PNS).

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Genetic Analysesmentioning

confidence: 99%

Section: Genetic Analysesmentioning

confidence: 99%

See 2 more Smart Citations

A mutation in an alternative untranslated exon of hexokinase 1 associated with Hereditary Motor and Sensory Neuropathy – Russe (HMSNR)

et al. 2009

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“…Consistent with its highly streamlined structure, the sperm flagellum does not have internal vesicles that function as stores of transporters or substrate. Rather, GLUT3 in the plasma membrane provides a "high throughput" capability by supplying substrate to the enzymes of glycolysis that are arrayed, at least in part, on the fibrous sheath, a cytoskeletal structure located immediately below the membrane (20,90,113,115,132). The high surface-area to volume of the flagellum maximizes the efficiency of the system, and then waste in the form of lactate can be removed by means of membrane monocarboxylate transporters (118).…”

Section: Glut3 In Murine Spermmentioning

confidence: 99%

The facilitative glucose transporter GLUT3: 20 years of distinction

Simpson

Dwyer

Malide

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

404

322

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Glucose metabolism is vital to most mammalian cells, and the passage of glucose across cell membranes is facilitated by a family of integral membrane transporter proteins, the GLUTs. There are currently 14 members of the SLC2 family of GLUTs, several of which have been the focus of this series of reviews. The subject of the present review is GLUT3, which, as implied by its name, was the third glucose transporter to be cloned (Kayano T, Fukumoto H, Eddy RL, Fan YS, Byers MG, Shows TB, Bell GI. J Biol Chem 263: [15245][15246][15247][15248] 1988) and was originally designated as the neuronal GLUT. The overriding question that drove the early work on GLUT3 was why would neurons need a separate glucose transporter isoform? What is it about GLUT3 that specifically suits the needs of the highly metabolic and oxidative neuron with its high glucose demand? More recently, GLUT3 has been studied in other cell types with quite specific requirements for glucose, including sperm, preimplantation embryos, circulating white blood cells, and an array of carcinoma cell lines. The last are sufficiently varied and numerous to warrant a review of their own and will not be discussed here. However, for each of these cases, the same questions apply. Thus, the objective of this review is to discuss the properties and tissue and cellular localization of GLUT3 as well as the features of expression, function, and regulation that distinguish it from the rest of its family and make it uniquely suited as the mediator of glucose delivery to these specific cells.neurons; sperm; preimplantation embryo; white blood cells GLUCOSE METABOLISM IS VITAL to most mammalian cells, and the passage of glucose across cell membranes is facilitated by a family of integral membrane transporter proteins, the GLUTs. There are currently 14 members of the SLC2 family of GLUTs, several of which have been the focus of this series of reviews. The subject of the present review is GLUT3 which, as implied by its name, was the third glucose transporter to be cloned (62) and was originally designated as the neuronal glucose transporter. Together with GLUT1, -2, and -4, it comprises the Class 1 group of transporters (For review see Refs. 15,81,121). With the cloning of GLUT3, it became apparent that the brain did not rely exclusively on GLUT1 and that GLUT3 was highly and specifically expressed by neurons. Thus, GLUT3 became the third facilitative glucose transporter isoform with unique characteristics suited for cell-specific expression and function. GLUT2 is ideally suited for expression in liver and pancreas due to its high K m for glucose; GLUT4 and its translocation from intracellular vesicles to the cell surface facilitates insulin-stimulated glucose uptake in insulin-sensitive cells: muscle and fat. The overriding question that drove the early work in GLUT3 in the brain was: why would neurons need a separate glucose transporter isoform; what is it about GLUT3 that specifically suits the needs of the highly metabolic and oxidative neuron with its high glucose demand?...

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SP22: A Novel Fertility Protein From a Highly Conserved Gene Family

WELCH,

BARBEE,

ROBERTS

et al. 1998

Journal of Andrology

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Three nucleotide sequences encoding SP22, a protein originally identified in detergent extracts of cauda epididymal sperm, were isolated from a rat testis cDNA library. While two of these cDNA sequences differed only in their 5′ untranslated regions, a third cDNA was predicted to contain an additional 13 amino acids of coding sequence. Amino acid sequences obtained following Edman degradation of purified SP22 protein and cDNA sequence data both indicated that SP22 was a member of a highly conserved and widely expressed gene family found in organisms as diverse as human and Escherichia coli. Interestingly, while a 1‐kb mRNA transcript was widely expressed in somatic tissues, a unique pattern of testicular expression was observed, including the appearance of a novel 1.5‐kb transcript and an increase in the abundance of the 1‐kb transcript during spermatogenic cell development. Anti‐SP22 peptide antiserum was shown to recognize a family of 22‐kDa proteins on western blots of detergent‐extracted cauda epididymal sperm protein, suggesting that multiple charge variants of SP22 coexist. Moreover, affinity‐purified anti‐SP22 peptide immunoglobulin localized in a highly specific manner to the anterior‐ventral surface of the equatorial segment of the sperm head. This is an extremely intriguing finding as SP22 was originally shown to be highly correlated with, and predictive of, the fertilizing ability of cauda epididymal sperm. Although no conclusive function has been attributed to any members of the SP22 gene family, the localization of SP22 over a discrete region of the sperm head suggests a pivotal role in sperm—egg interactions.

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Mouse spermatogenic cell-specific type 1 hexokinase (mHk1-s) transcripts are expressed by alternative splicing from themHk1 gene and the HK1-S protein is localized mainly in the sperm tail

Cited by 102 publications

References 42 publications

A mutation in an alternative untranslated exon of hexokinase 1 associated with Hereditary Motor and Sensory Neuropathy – Russe (HMSNR)

A mutation in an alternative untranslated exon of hexokinase 1 associated with Hereditary Motor and Sensory Neuropathy – Russe (HMSNR)

The facilitative glucose transporter GLUT3: 20 years of distinction

SP22: A Novel Fertility Protein From a Highly Conserved Gene Family

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