scholarly journals Sorting and Activity-Dependent Secretion of BDNF Require Interaction of a Specific Motif with the Sorting Receptor Carboxypeptidase E

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

scholarly journals Recycling of Raft-associated Prohormone Sorting Receptor Carboxypeptidase E Requires Interaction with ARF6

2003 ◽  
Vol 14 (11) ◽  
pp. 4448-4457 ◽  
Author(s):  
Irina Arnaoutova ◽  
Catherine L. Jackson ◽  
Omayma S. Al-Awar ◽  
Julie G. Donaldson ◽  
Y. Peng Loh
Keyword(s):  
Plasma Membrane ◽  
Lipid Raft ◽  
Endocrine Cells ◽  
Transmembrane Domain ◽  
Cytoplasmic Tail ◽  
Small Gtpase ◽  
Α Subunit ◽  
Carboxypeptidase E ◽  
Early Endosomes ◽  
Sorting Receptor

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.

scholarly journals Carboxypeptidase E Is a Regulated Secretory Pathway Sorting Receptor: Genetic Obliteration Leads to Endocrine Disorders in Cpefat Mice

Cell ◽  
1997 ◽  
Vol 88 (1) ◽  
pp. 73-83 ◽  
Author(s):  
David R Cool ◽  
Emmanuel Normant ◽  
Fu-sheng Shen ◽  
Hao-Chia Chen ◽  
Lewis Pannell ◽  
...  
Keyword(s):  
Secretory Pathway ◽  
Endocrine Disorders ◽  
Carboxypeptidase E ◽  
Sorting Receptor ◽  
Regulated Secretory Pathway

scholarly journals Carboxypeptidase E regulates Activity-dependent TrkB Neuronal surface Insertion and Hippocampal memory

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) ◽  
...  
Keyword(s):  
Carboxypeptidase E ◽  
Activity Dependent

scholarly journals SorCS1-mediated Sorting of Neurexin in Dendrites Maintains Presynaptic Function

2019 ◽  
Author(s):  
Luís F. Ribeiro ◽  
Ben Verpoort ◽  
Julie Nys ◽  
Kristel M. Vennekens ◽  
Keimpe D. Wierda ◽  
...  
Keyword(s):  
Protein Composition ◽  
Effector Protein ◽  
Synaptic Membrane ◽  
Surface Distribution ◽  
Recycling Endosomes ◽  
Surface Polarization ◽  
Presynaptic Function ◽  
Early Endosomes ◽  
Sorting Receptor ◽  
Activity Dependent

AbstractThe pre- and postsynaptic membranes comprising the synaptic junction differ in protein composition. The mechanisms that maintain the polarized distribution of synaptic membrane proteins are poorly understood. The sorting receptor SorCS1 is a critical trafficking regulator of neuronal receptors, including neurexin (Nrxn), a presynaptic adhesion molecule essential for synaptic transmission. We find that SorCS1 controls a balance between axonal and dendritic Nrxn1α surface levels. Newly synthesized Nrxn1α traffics to the somatodendritic surface, followed by endocytosis. SorCS1 interacts with the Rab11 effector protein Rab11FIP5/Rip11 to facilitate the transition of internalized Nrxn1α from early to recycling endosomes and bias Nrxn1α surface polarization toward the axon. In the absence of SorCS1, Nrxn1α accumulates in early endosomes and mis-polarizes to the dendritic surface, impairing presynaptic function. The axonal/dendritic balance of Nrxn1α surface distribution is activity-dependent, indicating that SorCS1-mediated sorting in somatodendritic endosomes dynamically controls Nrxn1α axonal surface polarization required for proper presynaptic function.

scholarly journals Sorting of carboxypeptidase E to the regulated secretory pathway requires interaction of its transmembrane domain with lipid rafts

2003 ◽  
Vol 369 (3) ◽  
pp. 453-460 ◽  
Author(s):  
Chun-Fa ZHANG ◽  
Savita DHANVANTARI ◽  
Hong LOU ◽  
Y. Peng LOH
Keyword(s):  
Fusion Protein ◽  
Lipid Rafts ◽  
Secretory Granule ◽  
Secretory Pathway ◽  
Full Length ◽  
Density Gradients ◽  
Carboxypeptidase E ◽  
Neuro2a Cells ◽  
Sorting Receptor ◽  
Regulated Secretory Pathway

Carboxypeptidase E (CPE) functions as a regulated secretory pathway sorting receptor for several prohormones, including pro-opiomelanocortin (POMC), proenkephalin and proinsulin. The association of CPE with lipid rafts in the trans-Golgi network and secretory granule membranes is necessary for its sorting receptor function. We now provide evidence that a domain within the C-terminal 25 residues of CPE functions as a signal for both raft association and the sorting of CPE to the regulated secretory pathway. A fusion protein containing the extracellular domain of the human interleukin-2 receptor Tac (N-Tac) and the C-terminal 25 amino acids of CPE was transfected into Neuro2A cells. This fusion protein floated in sucrose density gradients, indicating raft association, and co-localized with chromogranin A (CGA), a secretory granule marker. To define further a minimum sequence required for raft association and sorting, deletion mutants of CPE that lacked the C-terminal four or 15 residues (CPE-Δ4 and CPE-Δ15 respectively) were transfected into a clone of CPE-deficient Neuro2A cells. In contrast with full-length CPE, neither CPE-Δ4 nor CPE-Δ15 floated in sucrose density gradients. The sorting of both CPE-Δ4 and CPE-Δ15 to the regulated secretory pathway was impaired, as indicated by significantly increased basal secretion and a lack of response to stimulation. Additionally, there was a significant decrease in the co-localization of mutant CPE immunofluorescence with CGA when compared with full-length CPE. Finally, the sorting of the prohormone POMC to the regulated pathway was impaired in cells transfected with either CPE-Δ4 or CPE-Δ15. We conclude that the sorting of CPE to the regulated secretory pathway in endocrine cells is mediated by lipid rafts, and that the C-terminal four residues of CPE, i.e. Thr431-Leu-Asn-Phe434, are required for raft association and sorting.

Carboxypeptidase E, a Prohormone Sorting Receptor, Is Anchored to Secretory Granules via a C-Terminal Transmembrane Insertion†

Biochemistry ◽  
2002 ◽  
Vol 41 (1) ◽  
pp. 52-60 ◽  
Author(s):  
Savita Dhanvantari ◽  
Irina Arnaoutova ◽  
Chris R. Snell ◽  
Peter J. Steinbach ◽  
Kelli Hammond ◽  
...  
Keyword(s):  
Secretory Granules ◽  
Carboxypeptidase E ◽  
Sorting Receptor
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