scholarly journals Carboxypeptidase E Cytoplasmic Tail-Driven Vesicle Transport Is Key for Activity-Dependent Secretion of Peptide Hormones

2008 ◽  
Vol 22 (4) ◽  
pp. 989-1005 ◽  
Author(s):  
Joshua J. Park ◽  
Niamh X. Cawley ◽  
Y. Peng Loh
2010 ◽  
Vol 114 (3) ◽  
pp. 886-896 ◽  
Author(s):  
Hong Lou ◽  
Joshua J. Park ◽  
Niamh X. Cawley ◽  
Annahita Sarcon ◽  
Lei Sun ◽  
...  

Neuron ◽  
2005 ◽  
Vol 45 (2) ◽  
pp. 245-255 ◽  
Author(s):  
Hong Lou ◽  
Soo-Kyung Kim ◽  
Eugene Zaitsev ◽  
Chris R. Snell ◽  
Bai Lu ◽  
...  

2003 ◽  
Vol 14 (11) ◽  
pp. 4448-4457 ◽  
Author(s):  
Irina Arnaoutova ◽  
Catherine L. Jackson ◽  
Omayma S. Al-Awar ◽  
Julie G. Donaldson ◽  
Y. Peng Loh

Little is known about the molecular mechanism of recycling of intracellular receptors and lipid raft-associated proteins. Here, we have investigated the recycling pathway and internalization mechanism of a transmembrane, lipid raft-associated intracellular prohormone sorting receptor, carboxypeptidase E (CPE). CPE is found in the trans-Golgi network (TGN) and secretory granules of (neuro)endocrine cells. An extracellular domain of the IL2 receptor α-subunit (Tac) fused to the transmembrane domain and cytoplasmic tail of CPE (Tac-CPE25) was used as a marker to track recycling of CPE. We show in (neuro)endocrine cells, that upon stimulated secretory granule exocytosis, raft-associated Tac-CPE25 was rapidly internalized from the plasma membrane in a clathrin-independent manner into early endosomes and then transported through the endocytic recycling compartment to the TGN. A yeast two-hybrid screen and in vitro binding assay identified the CPE cytoplasmic tail sequence S472ETLNF477 as an interactor with active small GTPase ADP-ribosylation factor (ARF) 6, but not ARF1. Expression of a dominant negative, inactive ARF6 mutant blocked this recycling. Mutation of residues S472 or E473 to A in the cytoplasmic tail of CPE obliterated its binding to ARF6, and internalization from the plasma membrane of Tac-CPE25 mutated at S472 or E473 was significantly reduced. Thus, CPE recycles back to the TGN by a novel mechanism requiring ARF6 interaction and activity.


2013 ◽  
Vol 66 (3) ◽  
pp. 297 ◽  
Author(s):  
Feihua Cao ◽  
Christopher J. Easton

Peptide hormones with a C-terminal amide regulate numerous physiological processes and are associated with many disease states. Consequently, the key enzymes involved in their production, peptidylglycine α-amidating monooxygenase and carboxypeptidase E, have been studied intensively. This review surveys what is known about the enzymes themselves and their cofactors, as well as their substrates and competitive and mechanism-based inhibitors.


2017 ◽  
Vol 6 (4) ◽  
pp. R18-R38 ◽  
Author(s):  
Lin Ji ◽  
Huan-Tong Wu ◽  
Xiao-Yan Qin ◽  
Rongfeng Lan

Since discovery in 1982, carboxypeptidase E (CPE) has been shown to be involved in the biosynthesis of a wide range of neuropeptides and peptide hormones in endocrine tissues, and in the nervous system. This protein is produced from pro-CPE and exists in soluble and membrane forms. Membrane CPE mediates the targeting of prohormones to the regulated secretory pathway, while soluble CPE acts as an exopeptidase and cleaves C-terminal basic residues from peptide intermediates to generate bioactive peptides. CPE also participates in protein internalization, vesicle transport and regulation of signaling pathways. Therefore, in two types of CPE mutant mice, Cpefat/Cpefat and Cpe knockout, loss of normal CPE leads to a lot of disorders, including diabetes, hyperproinsulinemia, low bone mineral density and deficits in learning and memory. In addition, the potential roles of CPE and ΔN-CPE, an N-terminal truncated form, in tumorigenesis and diagnosis were also addressed. Herein, we focus on dissecting the pathophysiological roles of CPE in the endocrine and nervous systems, and related diseases.


2021 ◽  
pp. JN-RM-0236-21
Author(s):  
Na Li(娜李) ◽  
Shuai-Wen Teng(文滕帅) ◽  
Ling Zhao(玲赵) ◽  
Jing-Rui Li(瑞李敬) ◽  
Jia-Ling Xu(玲许佳) ◽  
...  

2015 ◽  
Vol 58 ◽  
pp. 115-131 ◽  
Author(s):  
Ayane Motomitsu ◽  
Shinichiro Sawa ◽  
Takashi Ishida

The ligand–receptor-based cell-to-cell communication system is one of the most important molecular bases for the establishment of complex multicellular organisms. Plants have evolved highly complex intercellular communication systems. Historical studies have identified several molecules, designated phytohormones, that function in these processes. Recent advances in molecular biological analyses have identified phytohormone receptors and signalling mediators, and have led to the discovery of numerous peptide-based signalling molecules. Subsequent analyses have revealed the involvement in and contribution of these peptides to multiple aspects of the plant life cycle, including development and environmental responses, similar to the functions of canonical phytohormones. On the basis of this knowledge, the view that these peptide hormones are pivotal regulators in plants is becoming increasingly accepted. Peptide hormones are transcribed from the genome and translated into peptides. However, these peptides generally undergo further post-translational modifications to enable them to exert their function. Peptide hormones are expressed in and secreted from specific cells or tissues. Apoplastic peptides are perceived by specialized receptors that are located at the surface of target cells. Peptide hormone–receptor complexes activate intracellular signalling through downstream molecules, including kinases and transcription factors, which then trigger cellular events. In this chapter we provide a comprehensive summary of the biological functions of peptide hormones, focusing on how they mature and the ways in which they modulate plant functions.


2001 ◽  
Vol 12 (1) ◽  
pp. 8-14
Author(s):  
Gertraud Teuchert-Noodt ◽  
Ralf R. Dawirs

Abstract: Neuroplasticity research in connection with mental disorders has recently bridged the gap between basic neurobiology and applied neuropsychology. A non-invasive method in the gerbil (Meriones unguiculus) - the restricted versus enriched breading and the systemically applied single methamphetamine dose - offers an experimental approach to investigate psychoses. Acts of intervening affirm an activity dependent malfunctional reorganization in the prefrontal cortex and in the hippocampal dentate gyrus and reveal the dopamine position as being critical for the disruption of interactions between the areas concerned. From the extent of plasticity effects the probability and risk of psycho-cognitive development may be derived. Advance may be expected from insights into regulatory mechanisms of neurogenesis in the hippocampal dentate gyrus which is obviously to meet the necessary requirements to promote psycho-cognitive functions/malfunctions via the limbo-prefrontal circuit.


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