---
_id: '2311'
abstract:
- lang: eng
  text: Inactivation of the mainly endosomal 2Cl-/H+- exchanger ClC-5 severely impairs
    endocytosis in renal proximal tubules and underlies the human kidney stone disorder
    Dent's disease. In heterologous expression systems, interaction of the E3 ubiquitin
    ligasesWWP2and Nedd4-2 with a "PY-motif" in the cytoplasmic C terminus
    of ClC-5 stimulates its internalization from the plasma membrane and may influence
    receptor-mediated endocytosis. We asked whether this interaction is relevant in
    vivo and generated mice in which the PY-motif was destroyed by a point mutation.
    Unlike ClC-5 knock-out mice, these knock-in mice displayed neither low molecular
    weight proteinuria nor hyperphosphaturia, and both receptor-mediated and fluid-phase
    endocytosis were normal. The abundances and localizations of the endocytic receptor
    megalin and of the Na+-coupled phosphate transporter NaPi-2a (Npt2) were not changed,
    either. To explore whether the discrepancy in results from heterologous expression
    studies might be due to heteromerization of ClC-5 with ClC-3 or ClC-4 in vivo,
    we studied knock-in mice additionally deleted for those related transporters.
    Disruption of neither ClC-3 nor ClC-4 led to proteinuria or impaired proximal
    tubular endocytosis by itself, nor in combination with the PY-mutant of ClC-5.
    Endocytosis of cells lacking ClC-5 was not impaired further when ClC-3 or ClC-4
    was additionally deleted. We conclude that ClC-5 is unique among CLC proteins
    in being crucial for proximal tubular endocytosis and that PY-motif-dependent
    ubiquitylation of ClC-5 is dispensable for this role.
author:
- first_name: Gesa
  full_name: Rickheit, Gesa
  last_name: Rickheit
- first_name: Lena
  full_name: Wartosch, Lena
  last_name: Wartosch
- first_name: Sven
  full_name: Schaffer, Sven
  last_name: Schaffer
- first_name: Sandra
  full_name: Stobrawa, Sandra M
  last_name: Stobrawa
- first_name: Gaia
  full_name: Gaia Novarino
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
- first_name: Stefanie
  full_name: Weinert, Stefanie
  last_name: Weinert
- first_name: Thomas
  full_name: Jentsch, Thomas J
  last_name: Jentsch
citation:
  ama: Rickheit G, Wartosch L, Schaffer S, et al. Role of ClC-5 in renal endocytosis
    is unique among ClC exchangers and does not require PY-motif-dependent ubiquitylation.
    <i>Journal of Biological Chemistry</i>. 2010;285(23):17595-17603. doi:<a href="https://doi.org/10.1074/jbc.M110.115600">10.1074/jbc.M110.115600</a>
  apa: Rickheit, G., Wartosch, L., Schaffer, S., Stobrawa, S., Novarino, G., Weinert,
    S., &#38; Jentsch, T. (2010). Role of ClC-5 in renal endocytosis is unique among
    ClC exchangers and does not require PY-motif-dependent ubiquitylation. <i>Journal
    of Biological Chemistry</i>. American Society for Biochemistry and Molecular Biology.
    <a href="https://doi.org/10.1074/jbc.M110.115600">https://doi.org/10.1074/jbc.M110.115600</a>
  chicago: Rickheit, Gesa, Lena Wartosch, Sven Schaffer, Sandra Stobrawa, Gaia Novarino,
    Stefanie Weinert, and Thomas Jentsch. “Role of ClC-5 in Renal Endocytosis Is Unique
    among ClC Exchangers and Does Not Require PY-Motif-Dependent Ubiquitylation.”
    <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and
    Molecular Biology, 2010. <a href="https://doi.org/10.1074/jbc.M110.115600">https://doi.org/10.1074/jbc.M110.115600</a>.
  ieee: G. Rickheit <i>et al.</i>, “Role of ClC-5 in renal endocytosis is unique among
    ClC exchangers and does not require PY-motif-dependent ubiquitylation,” <i>Journal
    of Biological Chemistry</i>, vol. 285, no. 23. American Society for Biochemistry
    and Molecular Biology, pp. 17595–17603, 2010.
  ista: Rickheit G, Wartosch L, Schaffer S, Stobrawa S, Novarino G, Weinert S, Jentsch
    T. 2010. Role of ClC-5 in renal endocytosis is unique among ClC exchangers and
    does not require PY-motif-dependent ubiquitylation. Journal of Biological Chemistry.
    285(23), 17595–17603.
  mla: Rickheit, Gesa, et al. “Role of ClC-5 in Renal Endocytosis Is Unique among
    ClC Exchangers and Does Not Require PY-Motif-Dependent Ubiquitylation.” <i>Journal
    of Biological Chemistry</i>, vol. 285, no. 23, American Society for Biochemistry
    and Molecular Biology, 2010, pp. 17595–603, doi:<a href="https://doi.org/10.1074/jbc.M110.115600">10.1074/jbc.M110.115600</a>.
  short: G. Rickheit, L. Wartosch, S. Schaffer, S. Stobrawa, G. Novarino, S. Weinert,
    T. Jentsch, Journal of Biological Chemistry 285 (2010) 17595–17603.
date_created: 2018-12-11T11:56:55Z
date_published: 2010-06-04T00:00:00Z
date_updated: 2021-01-12T06:56:42Z
day: '04'
doi: 10.1074/jbc.M110.115600
extern: 1
intvolume: '       285'
issue: '23'
month: '06'
page: 17595 - 17603
publication: Journal of Biological Chemistry
publication_status: published
publisher: American Society for Biochemistry and Molecular Biology
publist_id: '4618'
quality_controlled: 0
status: public
title: Role of ClC-5 in renal endocytosis is unique among ClC exchangers and does
  not require PY-motif-dependent ubiquitylation
type: journal_article
volume: 285
year: '2010'
...