IsoQC (QPCTL) knock-out mice suggest differential substrate conversion by glutaminyl cyclase isoenzymes

Biological Chemistry
Andreas BeckerStephan Schilling

Abstract

Secretory peptides and proteins are frequently modified by pyroglutamic acid (pE, pGlu) at their N-terminus. This modification is catalyzed by the glutaminyl cyclases QC and isoQC. Here, we decipher the roles of the isoenzymes by characterization of IsoQC-/- mice. These mice show a significant reduction of glutaminyl cyclase activity in brain and peripheral tissue, suggesting ubiquitous expression of the isoQC enzyme. An assay of substrate conversion in vivo reveals impaired generation of the pGlu-modified C-C chemokine ligand 2 (CCL2, MCP-1) in isoQC-/- mice. The pGlu-formation was also impaired in primary neurons, which express significant levels of QC. Interestingly, however, the formation of the neuropeptide hormone thyrotropin-releasing hormone (TRH), assessed by immunohistochemistry and hormonal analysis of hypothalamic-pituitary-thyroid axis, was not affected in isoQC-/-, which contrasts to QC-/-. Thus, the results reveal differential functions of isoQC and QC in the formation of the pGlu-peptides CCL2 and TRH. Substrates requiring extensive prohormone processing in secretory granules, such as TRH, are primarily converted by QC. In contrast, protein substrates such as CCL2 appear to be primarily converted by isoQC. The r...Continue Reading

References

Jun 1, 1995·Journal of Neuroendocrinology·T M BöckersT Pohl
Sep 13, 1996·The Journal of Biological Chemistry·I P Cruz, E A Nillni
Oct 6, 1997·Proceedings of the National Academy of Sciences of the United States of America·M YamadaM Mori
Oct 26, 1999·Endocrine Reviews·E A Nillni, K A Sevarino
Jan 31, 2004·Thyroid : Official Journal of the American Thyroid Association·Masanobu YamadaMasatomo Mori
Aug 3, 2005·Mammalian Genome : Official Journal of the International Mammalian Genome Society·M AugustinS Wattler
Sep 2, 2005·Proceedings of the National Academy of Sciences of the United States of America·Kai-Fa HuangAndrew H-J Wang
Jul 6, 2006·Biochimica Et Biophysica Acta·Nadia AmharrefMichel Manfait
Sep 29, 2006·Biochimica Et Biophysica Acta·Holger CynisHans-Ulrich Demuth
Aug 25, 2009·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Maike Hartlage-RübsamenSteffen Rossner
Oct 7, 2009·The FEBS Journal·Anett StephanStephan Schilling
Nov 20, 2009·Biochemistry·Franziska SeifertStephan Schilling
Sep 9, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Anca AlexandruStephan von Hörsten
Oct 4, 2011·The Journal of Biological Chemistry·Sadim JawharThomas A Bayer
Jun 3, 2014·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Corinna HöflingMaike Hartlage-Rübsamen

❮ Previous
Next ❯

Citations

May 17, 2017·Electrophoresis·Claudia SpahnStephan Schilling
Apr 21, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Maike Hartlage-RübsamenCorinna Höfling
Feb 6, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Janett KöppenStephan Schilling
Jul 10, 2019·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Dileep K Vijayan, Kam Y J Zhang
Dec 30, 2020·International Journal of Biological Macromolecules·K V DileepKam Y J Zhang
Nov 17, 2020·Drug Discovery Today·Wei-Bang YuJin-Jian Lu
Apr 27, 2021·Expert Opinion on Therapeutic Patents·Judite R M Coimbra, Jorge A R Salvador
May 19, 2021·Journal of Medicinal Chemistry·Chenshu XuHaiqiang Wu
Oct 6, 2021·Journal of Cancer Research and Clinical Oncology·Yu-Chi ChenJin-Jian Lu

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
Genotyping
enzymatic assay
electrophoresis
biopsies
ELISAs
ELISA

Software Mentioned

Bio1D
isoQC

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.