scholarly journals A Chaperone Cascade Sorts Proteins for Posttranslational Membrane Insertion into the Endoplasmic Reticulum

2010 ◽  
Vol 40 (1) ◽  
pp. 159-171 ◽  
Author(s):  
Fei Wang ◽  
Emily C. Brown ◽  
Gary Mak ◽  
Jimmy Zhuang ◽  
Vladimir Denic
2010 ◽  
Vol 10 (6) ◽  
pp. 639-647 ◽  
Author(s):  
María Angeles Juanes ◽  
Carlos Andrés Martínez-Garay ◽  
Juan Carlos Igual ◽  
María Carmen Bañó

2000 ◽  
Vol 11 (5) ◽  
pp. 1657-1672 ◽  
Author(s):  
Pascal Béguin ◽  
Udo Hasler ◽  
Olivier Staub ◽  
Käthi Geering

The molecular nature of determinants that mediate degradation of unassembled, polytopic subunits of oligomeric membrane proteins and their stabilization after partner subunit assembly is largely unknown. Expressing truncated Na,K-ATPase α subunits alone or together with β subunits, we find that in unassembled α subunits neither the four N-terminal transmembrane segments acting as efficient alternating signal anchor–stop transfer sequences nor the large, central cytoplasmic loop exposes any degradation signal, whereas poor membrane insertion efficiency of C-terminal membrane domains M5, M7, and M9 coincides with the transient exposure of degradation signals to the cytoplasmic side. β assembly with an α domain comprising at least D902 up to Y910 in the extracytoplasmic M7/M8 loop is necessary to stabilize Na,K-ATPase α subunits by favoring M7/M8 membrane pair formation and by protecting a degradation signal recognized from the endoplasmic reticulum (ER) lumenal side. Thus our results suggest that ER degradation of Na,K-ATPase α subunits is 1) mainly mediated by folding defects caused by inefficient membrane insertion of certain membrane domains, 2) a multistep process, which involves proteolytic and/or chaperone components acting from the ER lumenal side in addition to cytosolic, proteasome-related factors, and 3) prevented by partner subunit assembly because of direct protection and retrieval of degradation signals from the cytoplasm to the ER lumenal side. These results likely represent a paradigm for the ER quality control of unassembled, polytopic subunits of oligomeric membrane proteins.


2019 ◽  
Vol 20 (2) ◽  
pp. 334 ◽  
Author(s):  
Marina Blenski ◽  
Ralph Kehlenbach

LRRC59 (leucine-rich repeat-containing protein 59) is a tail-anchored protein with a single transmembrane domain close to its C-terminal end that localizes to the endoplasmic reticulum (ER) and the nuclear envelope. Here, we investigate the mechanisms of membrane integration of LRRC59 and its targeting to the inner nuclear membrane (INM). Using purified microsomes, we show that LRRC59 can be post-translationally inserted into ER-derived membranes. The TRC-pathway, a major route for post-translational membrane insertion, is not required for LRRC59. Like emerin, another tail-anchored protein, LRRC59 reaches the INM, as demonstrated by rapamycin-dependent dimerization assays. Using different approaches to inhibit importin α/β-dependent nuclear import of soluble proteins, we show that the classic nuclear transport machinery does not play a major role in INM-targeting of LRRC59. Instead, the size of the cytoplasmic domain of LRRC59 is an important feature, suggesting that targeting is governed by passive diffusion.


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