Alternative splicing of the mouse amelogenin primary RNA transcript

Simmer, James P.; Hu, C.-C.; Lau, Eduardo C.; Sarte, Patrick; Slavkin, Harold C.; Fincham, Alan G.

doi:10.1007/bf00310410

Cited by 95 publications

(60 citation statements)

References 55 publications

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“…Despite the large number of separate bands evident on polyacrylamide gels, about 90% of the protein is amelogenin (Termine et al, 1980). The reason there are so many bands of amelogenin is due primarily to proteolysis, although the expression of amelogenin isoforms from alternatively spliced transcripts also plays a role (Salido et al, 1992;Simmer et al, 1994). The apparently unchanging pattern of enamel matrix bands in successive secretory stage samples is the result of a steady state, where the amount of a particular protein is determined by its rate of generation (by proteolysis or secretion) and its rate of elimination (by further proteolysis or reabsorption).…”

Section: Stages Of Enamel Formationmentioning

confidence: 99%

Functions of KLK4 and MMP-20 in dental enamel formation

Papagerakis²,

Yamakoshi

et al. 2008

BCHM

221

190

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Two proteases are secreted into the enamel matrix of developing teeth. The early protease is enamelysin . The late protease is kallikrein 4 (KLK4). Mutations in MMP20 and KLK4 both cause autosomal recessive amelogenesis imperfecta, a condition featuring soft, porous enamel containing residual protein. MMP-20 is secreted along with enamel proteins by secretory stage ameloblasts. Enamel protein cleavage products accumulate in the space between the crystal ribbons, helping to support them. MMP-20 steadily cleaves accumulated enamel proteins, so their concentration decreases with depth. Kallikrein 4 is secreted by transition and maturation stage ameloblasts. KLK4 aggressively degrades the retained organic matrix following the termination of enamel protein secretion. The principle functions of MMP-20 and KLK4 in dental enamel formation are to facilitate the orderly replacement of organic matrix with mineral, generating an enamel layer that is harder, less porous, and unstained by retained enamel proteins.

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Section: Stages Of Enamel Formationmentioning

confidence: 99%

Functions of KLK4 and MMP-20 in dental enamel formation

Papagerakis²,

Yamakoshi

et al. 2008

BCHM

221

190

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“…At least 15 amelogenin messages have been reported due to alternative splicing of the primary RNA transcript of the single murine X-chromosomal amelogenin gene 22,23 . A Ychromosomal amelogenin gene has not been identified in mice.…”

Section: Mouse Models For Amelogenesis Imperfectamentioning

confidence: 99%

The Amelogenin Proteins and Enamel Development in Humans and Mice

Gibson

2011

Journal of Oral Biosciences

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Before a tooth erupts into the oral cavity, the mineralized enamel and dentin layers begin to develop. During these early stages of enamel formation, an abundant group of proteins known as amelogenins are secreted by ameloblast cells within the developing tooth. These proteins are required for the enamel layer to reach its normal thickness and attain its intricate structure. Human patients with amelogenin gene mutations have a condition referred to as amelogenesis imperfecta, and we have analyzed human gene defects so that we can recreate them in mice. We have generated mice with a null amelogenin mutation where no amelogenin is produced, mice that over-express normal and mutated amelogenins, and over-expressors have been mated to null mice for rescue experiments. Because there are at least 15 messages that are alternatively spliced from a single amelogenin primary RNA transcript, these approaches have begun to reveal the functions of individual amelogenin proteins during enamel development. Finally, amelogenins are processed by carefully regulated proteolytic digestion leading to many additional amelogenin peptides and it is likely that protein function is altered during this developmental process. We have also had some surprises, as one of our mouse models develops odontogenic tumors, and we know now that some of the amelogenins are expressed in other regions of the body outside of the oral cavity, and may have a role in signal transduction.

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“…In mice, ameloblasts generate at least 15 alternative mRNA splicing isoforms of amelogenin encompassing exon 1 to exon 9 1,2) , which encode various lengths of amino acid sequences. M180 is most abundant amelogenin isoform, in which the exon 4 is excluded from the full-length transcript of M194.…”

Section: Introductionmentioning

confidence: 99%

“…M180 is most abundant amelogenin isoform, in which the exon 4 is excluded from the full-length transcript of M194. The leucine-rich amelogenin peptide (LRAP) is one of two most abundant amelogenin isoforms, and was first proposed to explain the presence of alternative splice isoforms in amelogenin 1) and is also known as M59 3) or A-4 4) . These larger secreted amelogenins are degraded into various smaller amelogenin peptides by proteinases such as matrix metalloproteinase-20 (MMP-20) and kallikrein 4 (KLK4) during enamel mineralization 5) and organic matrices including amelogenin in the enamel are almost completely removed during enamel mineralization before tooth eruption.…”

Section: Introductionmentioning

confidence: 99%

Effects of a Chemically Synthesized Leucine-Rich Amelogenin Peptide (csLRAP) on Chondrogenic and Osteogenic Cells

Matsuda

Hatakeyama

Nakashima

et al. 2017

J. Hard Tissue Biology.

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Amelogenin is one of the enamel matrices secreted by ameloblasts and is known to have at least 15 alternative mRNA splicing isoforms. The leucine rich amelogenin peptide (LRAP) is one of most abundant amelogenin isoforms and numerous studies have shown that amelogenin peptides including LRAP, are expressed in cartilage and bone. Lysosome-associated membrane protein-1 (LAMP-1) has been identified as amelogenin binding partner, however, the mechanism of action for LRAP in chondrogenesis or osteogenesis is still unclear. This study aimed to assay the effect of chemically synthesized LRAP (csLRAP) on chondrogenic or osteogenic differentiation with the involvement of LAMP-1. The csLRAP used in this study was generated by F-moc solid phase chemistry based on the mouse LRAP amino acid sequence and was added to the culture medium of the chondrogenic cells, ATDC5 and the osteoblast cells, MC3T3-E1. Both chondrogenic and osteoblast cells, in which an immunopositive reaction to LAMP-1 antibody was observed by immunocytochemistry, showed significant suppression in cell number in the presence of csLRAP at 10 g/ml compared to that in control, but this effect was rescued in the presence of LAMP-1 antibody. On the other hand, the intensity of alcian blue staining in chondrogenic cells and alizarin red staining in osteoblast cells was significantly increased in the presence of csLRAP at a dose of 10 g/ml after 4 weeks culture, and this effect was suppressed in the presence LAMP-1 antibody. Moreover, the chondrogenic or osteogenic differentiation marker genes including Sox9, Type II Collagen, Type X Collagen, Runx2, Alkaline Phosphatase, and Type I Collagen, were upregulated in the presence of csLRAP after one week of culture and were suppressed in the presence of LAMP-1 antibody. These results suggest that csLRAP could promote osteogenic and chondrogenic differentiation in vitro, and that LAMP-1 may be involved in the differentiation and proliferation of these cells.

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Alternative splicing of the mouse amelogenin primary RNA transcript

Cited by 95 publications

References 55 publications

Functions of KLK4 and MMP-20 in dental enamel formation

Functions of KLK4 and MMP-20 in dental enamel formation

The Amelogenin Proteins and Enamel Development in Humans and Mice

Effects of a Chemically Synthesized Leucine-Rich Amelogenin Peptide (csLRAP) on Chondrogenic and Osteogenic Cells

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