ERp29 Restricts Connexin43 Oligomerization in the Endoplasmic Reticulum

被引：69

作者：

Das, Shamie ^{[1
]}

Smith, Tekla D. ^{[1
]}

Das Sarma, Jayasri ^{[3
]}

Ritzenthaler, Jeffrey D. ^{[1
]}

Maza, Jose ^{[1
]}

Kaplan, Benjamin E. ^{[1
]}

Cunningham, Leslie A. ^{[1
]}

Suaud, Laurence ^{[4
,5
]}

Hubbard, Michael J. ^{[6
]}

Rubenstein, Ronald C. ^{[4
,5
]}

Koval, Michael ^{[1
,2
]}

机构：

[1] Emory Univ, Sch Med, Dept Med, Div Pulm Allergy & Crit Care Med, Atlanta, GA 30322 USA

[2] Emory Univ, Sch Med, Dept Cell Biol, Atlanta, GA 30322 USA

[3] Indian Inst Sci Educ & Res, Neurosci Grp, Kolkata 700106, India

[4] Univ Penn, Sch Med, Childrens Hosp Philadelphia, Div Pulm Med, Philadelphia, PA 19104 USA

[5] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA

[6] Univ Melbourne, Dept Paediat, Melbourne, Vic 3052, Australia

来源：

MOLECULAR BIOLOGY OF THE CELL | 2009年 / 20卷 / 10期

基金：

美国国家卫生研究院;

关键词：

JUNCTIONAL INTERCELLULAR COMMUNICATION; GAP-JUNCTION; SODIUM; 4-PHENYLBUTYRATE; FUNCTIONAL-ANALYSIS; CRYSTAL-STRUCTURE; PLASMA-MEMBRANES; QUALITY-CONTROL; LIFE-CYCLE; PROTEIN; EXPRESSION;

D O I：

10.1091/mbc.E08-07-0790

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Connexin43 (Cx43) is a gap junction protein that forms multimeric channels that enable intercellular communication through the direct transfer of signals and metabolites. Although most multimeric protein complexes form in the endoplasmic reticulum (ER), Cx43 seems to exit from the ER as monomers and subsequently oligomerizes in the Golgi complex. This suggests that one or more protein chaperones inhibit premature Cx43 oligomerization in the ER. Here, we provide evidence that an ER-localized, 29-kDa thioredoxin-family protein (ERp29) regulates Cx43 trafficking and function. Interfering with ERp29 function destabilized monomeric Cx43 oligomerization in the ER, caused increased Cx43 accumulation in the Golgi apparatus, reduced transport of Cx43 to the plasma membrane, and inhibited gap junctional communication. ERp29 also formed a specific complex with monomeric Cx43. Together, this supports a new role for ERp29 as a chaperone that helps stabilize monomeric Cx43 to enable oligomerization to occur in the Golgi apparatus.

引用

页码：2593 / 2604

页数：12

共 68 条

[11] Identification of rab20 as a potential regulator of connexin43 trafficking [J].

Das Sarma, Jayasri ;

Kaplan, Benjamin E. ;

Willemsen, Dounia ;

Koval, Michael .

CELL COMMUNICATION AND ADHESION, 2008, 15 (1-2) :65-74

[12] Regulation of heterotypic claudin compatibility [J].

Daugherty, Brandy L. ;

Ward, Christina ;

Smith, Tekla ;

Ritzenthaler, Jeffrey D. ;

Koval, Michael .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (41) :30005-30013

[13] Disruption of gap junctional intercellular communication by lindane is associated with aberrant localization of connexin43 and zonula occludens-1 in 42GPA9 Sertoli cells [J].

Defamie, N ;

Mograbi, B ;

Roger, C ;

Cronier, L ;

Malassine, A ;

Brucker-Davies, F ;

Fenichel, P ;

Segretain, D ;

Pointis, G .

CARCINOGENESIS, 2001, 22 (09) :1537-1542

[14] Molecular cloning of ERp29, a novel and widely expressed resident of the endoplasmic reticulum [J].

Demmer, J ;

Zhou, CM ;

Hubbard, MJ .

FEBS LETTERS, 1997, 402 (2-3) :145-150

[15] Quality control in the endoplasmic reticulum [J].

Ellgaard, L ;

Helenius, A .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2003, 4 (03) :181-191

[16] A Cα model for the transmembrane α helices of gap junction intercellular channels [J].

Fleishman, SJ ;

Unger, VM ;

Yeager, M ;

Ben-Tal, N .

MOLECULAR CELL, 2004, 15 (06) :879-888

[17] The pattern of disulfide linkages in the extracellular loop regions of connexin 32 suggests a model for the docking interface of gap junctions [J].

Foote, CI ;

Zhou, L ;

Zhu, X ;

Nicholson, BJ .

JOURNAL OF CELL BIOLOGY, 1998, 140 (05) :1187-1197

[18] Selective permeability of gap junction channels [J].

Goldberg, GS ;

Valiunas, V ;

Brink, PR .

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 2004, 1662 (1-2) :96-101

[19] Disruption of alpha(3) connexin gene leads to proteolysis and cataractogenesis in mice [J].

Gong, XH ;

Li, E ;

Klier, G ;

Huang, QL ;

Wu, Y ;

Lei, H ;

Kumar, NM ;

Horwitz, J ;

Gilula, NB .

CELL, 1997, 91 (06) :833-843

[20]

Gong XH, 1999, DEV GENET, V24, P27, DOI 10.1002/(SICI)1520-6408(1999)24:1/2<27::AID-DVG4>3.3.CO

← 1 2 3 4 5 6 7 →