Quality control of nonstop membrane proteins at the ER membrane and in the cytosol

The tubular network of the endoplasmic reticulum (ER) is formed by connecting ER tubules through three-way junctions. Two classes of the conserved ER membrane proteins, atlastins and lunapark, have been shown to reside at the three-way junctions so far and be involved in the generation and stabilization of the three-way junctions. In this study, we report TMCC3 (transmembrane and coiled-coil domain family 3), a member of the TEX28 family, as another ER membrane protein that resides at the three-way junctions in mammalian cells. When the TEX28 family members were transfected into U2OS cells, TMCC3 specifically localized at the three-way junctions in the peripheral ER. TMCC3 bound to atlastins through the C-terminal transmembrane domains. A TMCC3 mutant lacking the N-terminal coiled-coil domain abolished localization to the three-way junctions, suggesting that TMCC3 localized independently of binding to atlastins. TMCC3 knockdown caused a decrease in the number of three-way junctions and expansion of ER sheets, leading to a reduction of the tubular ER network in U2OS cells. The TMCC3 knockdown phenotype was partially rescued by the overexpression of atlastin-2, suggesting that TMCC3 knockdown would decrease the activity of atlastins. These results indicate that TMCC3 localizes at the three-way junctions for the proper tubular ER network.

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Septin-dependent compartmentalization of the endoplasmic reticulum during yeast polarized growth

The Journal of Cell Biology ◽

10.1083/jcb.200412143 ◽

2005 ◽

Vol 169 (6) ◽

pp. 897-908 ◽

Cited By ~ 108

Author(s):

Cosima Luedeke ◽

Stéphanie Buvelot Frei ◽

Ivo Sbalzarini ◽

Heinz Schwarz ◽

Anne Spang ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Plasma Membrane ◽

Membrane Proteins ◽

Diffusion Barriers ◽

Yeast Cells ◽

Dependent Manner ◽

Protein Diffusion ◽

Ultrastructural Studies ◽

Bud Neck ◽

Er Membrane

Polarized cells frequently use diffusion barriers to separate plasma membrane domains. It is unknown whether diffusion barriers also compartmentalize intracellular organelles. We used photobleaching techniques to characterize protein diffusion in the yeast endoplasmic reticulum (ER). Although a soluble protein diffused rapidly throughout the ER lumen, diffusion of ER membrane proteins was restricted at the bud neck. Ultrastructural studies and fluorescence microscopy revealed the presence of a ring of smooth ER at the bud neck. This ER domain and the restriction of diffusion for ER membrane proteins through the bud neck depended on septin function. The membrane-associated protein Bud6 localized to the bud neck in a septin-dependent manner and was required to restrict the diffusion of ER membrane proteins. Our results indicate that Bud6 acts downstream of septins to assemble a fence in the ER membrane at the bud neck. Thus, in polarized yeast cells, diffusion barriers compartmentalize the ER and the plasma membrane along parallel lines.

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HRDGene Dependence of Endoplasmic Reticulum-associated Degradation

Molecular Biology of the Cell ◽

10.1091/mbc.11.5.1697 ◽

2000 ◽

Vol 11 (5) ◽

pp. 1697-1708 ◽

Cited By ~ 84

Author(s):

Sharon Wilhovsky ◽

Richard Gardner ◽

Randolph Hampton

Keyword(s):

Endoplasmic Reticulum ◽

Membrane Proteins ◽

Protein Degradation ◽

Degradation Pathway ◽

Encoded Proteins ◽

Absolute Dependence ◽

Coa Reductase ◽

Ubiquitin Conjugating Enzymes ◽

Er Membrane

Work from several laboratories has indicated that many different proteins are subject to endoplasmic reticulum (ER) degradation by a common ER-associated machinery. This machinery includes ER membrane proteins Hrd1p/Der3p and Hrd3p and the ER-associated ubiquitin-conjugating enzymes Ubc7p and Ubc6p. The wide variety of substrates for this degradation pathway has led to the reasonable hypothesis that the HRD (Hmg CoA reductase degradation) gene-encoded proteins are generally involved in ER protein degradation in eukaryotes. We have tested this model by directly comparing the HRD dependency of the ER-associated degradation for various ER membrane proteins. Our data indicated that the role of HRD genes in protein degradation, even in this highly defined subset of proteins, can vary from absolute dependence to complete independence. Thus, ER-associated degradation can occur by mechanisms that do not involve Hrd1p or Hrd3p, despite their apparently broad envelope of substrates. These data favor models in which the HRD gene-encoded proteins function as specificity factors, such as ubiquitin ligases, rather than as factors involved in common aspects of ER degradation.

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Recycling of ER membrane proteins

Trends in Cell Biology ◽

10.1016/0962-8924(93)90120-p ◽

1993 ◽

Vol 3 (7) ◽

pp. 229

Author(s):

M.R. Jackson ◽

T. Nilsson ◽

P.A. Peterson

Keyword(s):

Membrane Proteins ◽

Er Membrane

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Quality control of membrane proteins in mitochondria

10.1240/sav_gbm_2002_h_000022 ◽

2002 ◽

Vol 2002 (Fall) ◽

Cited By ~ 4

Author(s):

Thomas Langer

Keyword(s):

Quality Control ◽

Membrane Proteins

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Periplasmic quality control in biogenesis of outer membrane proteins

Biochemical Society Transactions ◽

10.1042/bst20140217 ◽

2015 ◽

Vol 43 (2) ◽

pp. 133-138 ◽

Cited By ~ 18

Author(s):

Zhi Xin Lyu ◽

Xin Sheng Zhao

Keyword(s):

Quality Control ◽

Membrane Proteins ◽

Outer Membrane ◽

Outer Membrane Proteins ◽

Diverse Range ◽

Multifunctional Protein ◽

Proposed Model ◽

Periplasmic Proteins ◽

Basic Functions ◽

Biochemical Analyses

The β-barrel outer membrane proteins (OMPs) are integral membrane proteins that reside in the outer membrane of Gram-negative bacteria and perform a diverse range of biological functions. Synthesized in the cytoplasm, OMPs must be transported across the inner membrane and through the periplasmic space before they are assembled in the outer membrane. In Escherichia coli, Skp, SurA and DegP are the most prominent factors identified to guide OMPs across the periplasm and to play the role of quality control. Although extensive genetic and biochemical analyses have revealed many basic functions of these periplasmic proteins, the mechanism of their collaboration in assisting the folding and insertion of OMPs is much less understood. Recently, biophysical approaches have shed light on the identification of the intricate network. In the present review, we summarize recent advances in the characterization of these key factors, with a special emphasis on the multifunctional protein DegP. In addition, we present our proposed model on the periplasmic quality control in biogenesis of OMPs.

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AAA proteases of mitochondria: quality control of membrane proteins and regulatory functions during mitochondrial biogenesis

Biochemical Society Transactions ◽

10.1042/bst0290431 ◽

2001 ◽

Vol 29 (4) ◽

pp. 431-436 ◽

Cited By ~ 74

Author(s):

T. Langer ◽

M. Käser ◽

C. Klanner ◽

K. Leonhard

Keyword(s):

Quality Control ◽

Membrane Proteins ◽

Matrix Space ◽

Inner Membrane ◽

Membrane Surfaces ◽

Mitochondrial Inner Membrane ◽

Catalytic Sites ◽

The Matrix ◽

The Stability ◽

Regulatory Functions

An ubiquitous and conserved proteolytic system regulates the stability of mitochondrial inner membrane proteins. Two AAA proteases with catalytic sites at opposite membrane surfaces form a membrane-integrated quality control system and exert crucial functions during the biogenesis of mitochondria. Their activity is modulated by another membrane-protein complex that is composed of prohibitins. Peptides generated upon proteolysis in the matrix space are transported across the inner membrane by an ATP-binding cassette transporter. The function of these conserved components is discussed in the present review.

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