Ca<sup>2+</sup>-calmodulin inhibits tail-anchored protein insertion into the mammalian endoplasmic reticulum membrane

Haßdenteufel, Sarah; Schäuble, Nico; Cassella, Patrizia; Leznicki, Pawel; Müller, Ann-Kristin; High, Stephen; Jung, Martin; Zimmermann, Richard

doi:10.1016/j.febslet.2011.10.008

Cited by 24 publications

(20 citation statements)

References 35 publications

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“…For example, SRP was shown to target clients with a canonical N‐terminal signal sequence as well as tail‐anchored protein synaptobrevin 2 . Also, cytosolic chaperone calmodulin was shown to promote posttranslational membrane targeting of small secretory proteins while inhibiting the insertion of various TA . Studies addressing biogenesis of tail‐anchored and short secretory clients in vivo using tissue‐specific WRB (hepatocytes, cardiomyocytes) or TRC40 (pancreatic β‐cells) gene knockouts demonstrated heterogeneous, cell‐type‐specific requirements for proper protein topogenesis of different such precursors .…”

Section: Discussionmentioning

confidence: 99%

hSnd2 protein represents an alternative targeting factor to the endoplasmic reticulum in human cells

et al. 2017

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Recently, understanding of protein targeting to the endoplasmic reticulum (ER) was expanded by the discovery of multiple pathways that function in parallel to the signal recognition particle (SRP). Guided entry of tail-anchored proteins and SRP independent (SND) are two such targeting pathways described in yeast. So far, no human SND component is functionally characterized. Here, we report hSnd2 as the first constituent of the human SND pathway able to support substrate-specific protein targeting to the ER. Similar to its yeast counterpart, hSnd2 is assumed to function as a membrane-bound receptor preferentially targeting precursors carrying C-terminal transmembrane domains. Our genetic and physical interaction studies show that hSnd2 is part of a complex network of targeting and translocation that is dynamically regulated.

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Section: Discussionmentioning

confidence: 99%

hSnd2 protein represents an alternative targeting factor to the endoplasmic reticulum in human cells

et al. 2017

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“…Thus, low cellular ATP‐levels cause SRP‐independent transport to stop, while allowing SRP‐dependent transport to continue . On the other hand, when certain precursor polypeptides, such as at least some of the small ones, depend on Ca 2+ ‐CaM, their import – in contrast to the SRP/SR‐dependent one – can be regulated in a Ca 2+ ‐dependent fashion . Furthermore, when certain precursor proteins depend on allosteric Sec61‐channel effectors, such as the Sec62/Sec63‐complex, their ER import can be regulated independently from the import of Sec62/Sec63‐independent precursors.…”

Section: What Is the Point Of Having Small Presecretory Proteins?mentioning

confidence: 99%

ER import of small human presecretory proteins: components and mechanisms

et al. 2019

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Protein transport into the mammalian endoplasmic reticulum (ER) used to be seen as strictly cotranslational, that is temporarily and mechanistically coupled to protein synthesis. In the course of the last decades, however, several classes of precursors of soluble and membrane proteins were found to be post‐translationally imported into the ER, without any involvement of the ribosome. The first such class to be identified were the small presecretory proteins; tail‐anchored membrane proteins followed next. In both classes, the inherent address tag is released from the translating ribosome before the initiation of ER import, as part of the fully synthesized precursor. In small presecretory proteins, the information for ER targeting and ‐translocation via the polypeptide‐conducting Sec61‐channel is encoded by a classical N‐terminal signal peptide, which is released from the ribsosome before targeting due to the small size of the full‐length precursor. Here, we discuss the current state of research on targeting and translocation of small presecretory proteins into the mammalian ER. In closing, we present a unifying hypothesis for ER protein translocation in terms of an energy diagram for Sec61‐channel gating.

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“…Calmodulin (CaM) is an important calcium sensor, which has been previously shown to interact with several membrane receptors [38][39][40][41]. Here we identified several amino acids located within or downstream of the SEC24 interaction motif of GlyT1, which are structurally important for the calcium dependent interaction of the transporter C-terminus with calmodulin in vitro.…”

Section: Introductionmentioning

confidence: 94%

Calcium Dependent Interaction of Calmodulin with the GlyT1 C-terminus

2014

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The cytoplasmic regions of neurotransmitter transporters play an important role in their trafficking. This process is, to a high extent, tuned by calcium and calcium binding proteins, but the exact molecular connection are still not fully understood. In this work we found that the C-terminal region of the mouse glycine transporter GlyT1b is able to specifically interact with calmodulin in the presence of calcium. We found that several GlyT1 C-terminal mutations, including those in the ER retention signal, either eliminate or increase calmodulin interaction in vitro. In tissue-culture-expressed GlyT1 at least two of these mutations altered the sensitivity of GlyT1 surface expression and glycine uptake to calmodulin antagonists. These results suggest the possible involvement of calmodulin or calmodulin-like interactions in the regulation of GlyT1C-mediated transporter trafficking.

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Ca²⁺-calmodulin inhibits tail-anchored protein insertion into the mammalian endoplasmic reticulum membrane

Cited by 24 publications

References 35 publications

hSnd2 protein represents an alternative targeting factor to the endoplasmic reticulum in human cells

hSnd2 protein represents an alternative targeting factor to the endoplasmic reticulum in human cells

ER import of small human presecretory proteins: components and mechanisms

Calcium Dependent Interaction of Calmodulin with the GlyT1 C-terminus

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Ca2+-calmodulin inhibits tail-anchored protein insertion into the mammalian endoplasmic reticulum membrane

Cited by 24 publications

References 35 publications

hSnd2 protein represents an alternative targeting factor to the endoplasmic reticulum in human cells

hSnd2 protein represents an alternative targeting factor to the endoplasmic reticulum in human cells

ER import of small human presecretory proteins: components and mechanisms

Calcium Dependent Interaction of Calmodulin with the GlyT1 C-terminus

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Ca²⁺-calmodulin inhibits tail-anchored protein insertion into the mammalian endoplasmic reticulum membrane