Esben Skipper Sørensen

Human sorCS1 binds sortilin and hampers its cellular functions

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Human sorCS1 binds sortilin and hampers its cellular functions. / Larsen, Jakob Vejby; Hermey, Guido; Sørensen, Esben Skipper; Prabakaran, Thaneas; Christensen, Erik Ilsø; Gliemann, Jørgen; Madsen, Peder; Petersen, Claus Munck.

In: Biochemical Journal, Vol. 457, No. 2, 16.01.2014, p. 277–288.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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Larsen, Jakob Vejby et al. "Human sorCS1 binds sortilin and hampers its cellular functions". Biochemical Journal. 2014, 457(2). 277–288. https://doi.org/10.1042/BJ20130386

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Larsen, Jakob Vejby ; Hermey, Guido ; Sørensen, Esben Skipper ; Prabakaran, Thaneas ; Christensen, Erik Ilsø ; Gliemann, Jørgen ; Madsen, Peder ; Petersen, Claus Munck. / Human sorCS1 binds sortilin and hampers its cellular functions. In: Biochemical Journal. 2014 ; Vol. 457, No. 2. pp. 277–288.

Bibtex

@article{9c9eaf270f5449dca73c4298eae5217f,
title = "Human sorCS1 binds sortilin and hampers its cellular functions",
abstract = "Sortilin and sorCS1, both members of the Vps10p-D receptor family, are synthesized as precursor proteins and are converted to their mature form by enzymatic cleavage of a short N-terminal propeptide. SorCS1 does not bind its propeptide, but sortilin is able to bind not just its own propeptide but also that of sorCS1. Here we show that the propeptide region of sorCS1 contains two separate sites for binding to sortilin and that only one of these sites is removed from human (as opposed to mouse) sorCS1 during processing. This leaves mature human sorCS1 with a sortilin-binding N-terminus, which allows complex formation between the two receptors in solution and on cell membranes. Furthermore, we find that the interaction with sorCS1 has a pronounced effect on sortilins ability to mediate cellular uptake of alternative ligands, and to hamper its facilitation of CNTF signaling and induction of phosphorylated STAT3. Thus, the present findings reveal a novel regulatory mechanism and suggest an entirely new role of sorCS1 as a modulator of sortilin function.",
author = "Larsen, {Jakob Vejby} and Guido Hermey and S{\o}rensen, {Esben Skipper} and Thaneas Prabakaran and Christensen, {Erik Ils{\o}} and J{\o}rgen Gliemann and Peder Madsen and Petersen, {Claus Munck}",
year = "2014",
month = jan,
day = "16",
doi = "10.1042/BJ20130386",
language = "English",
volume = "457",
pages = "277–288",
journal = "Biochemical Journal",
issn = "0264-6021",
publisher = "Portland Press Ltd.",
number = "2",

}

RIS

TY - JOUR

T1 - Human sorCS1 binds sortilin and hampers its cellular functions

AU - Larsen, Jakob Vejby

AU - Hermey, Guido

AU - Sørensen, Esben Skipper

AU - Prabakaran, Thaneas

AU - Christensen, Erik Ilsø

AU - Gliemann, Jørgen

AU - Madsen, Peder

AU - Petersen, Claus Munck

PY - 2014/1/16

Y1 - 2014/1/16

N2 - Sortilin and sorCS1, both members of the Vps10p-D receptor family, are synthesized as precursor proteins and are converted to their mature form by enzymatic cleavage of a short N-terminal propeptide. SorCS1 does not bind its propeptide, but sortilin is able to bind not just its own propeptide but also that of sorCS1. Here we show that the propeptide region of sorCS1 contains two separate sites for binding to sortilin and that only one of these sites is removed from human (as opposed to mouse) sorCS1 during processing. This leaves mature human sorCS1 with a sortilin-binding N-terminus, which allows complex formation between the two receptors in solution and on cell membranes. Furthermore, we find that the interaction with sorCS1 has a pronounced effect on sortilins ability to mediate cellular uptake of alternative ligands, and to hamper its facilitation of CNTF signaling and induction of phosphorylated STAT3. Thus, the present findings reveal a novel regulatory mechanism and suggest an entirely new role of sorCS1 as a modulator of sortilin function.

AB - Sortilin and sorCS1, both members of the Vps10p-D receptor family, are synthesized as precursor proteins and are converted to their mature form by enzymatic cleavage of a short N-terminal propeptide. SorCS1 does not bind its propeptide, but sortilin is able to bind not just its own propeptide but also that of sorCS1. Here we show that the propeptide region of sorCS1 contains two separate sites for binding to sortilin and that only one of these sites is removed from human (as opposed to mouse) sorCS1 during processing. This leaves mature human sorCS1 with a sortilin-binding N-terminus, which allows complex formation between the two receptors in solution and on cell membranes. Furthermore, we find that the interaction with sorCS1 has a pronounced effect on sortilins ability to mediate cellular uptake of alternative ligands, and to hamper its facilitation of CNTF signaling and induction of phosphorylated STAT3. Thus, the present findings reveal a novel regulatory mechanism and suggest an entirely new role of sorCS1 as a modulator of sortilin function.

U2 - 10.1042/BJ20130386

DO - 10.1042/BJ20130386

M3 - Journal article

C2 - 24128306

VL - 457

SP - 277

EP - 288

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 2

ER -