Membrane Proteins of the Endoplasmic Reticulum Induce High-Curvature Tubules

Hu, Junjie; Shibata, Yoko; Voss, Christiane; Shemesh, Tom; Li, Zongli; Coughlin, Margaret; Kozlov, Michael M.; Rapoport, Tom A.; Prinz, William A.

doi:10.1126/science.1153634

Cited by 393 publications

(502 citation statements)

References 23 publications

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“…. As shown previously by others, GFPRtn4HD is significantly enriched during interphase in highly curved regions of the ER such as the tubules and the edges of the cisternae; it is much less abundant in the flatter portions of the ER cisternae and in the nuclear envelope Hu et al, 2008;Shibata et al, 2008) ( Figure 5A). As a result, the overall Pearson's r is relatively low: 0.83 Ϯ 0.02 (mean Ϯ SD; n ϭ 3) for the 3D colocalization of GFP-Rtn4HD and cherry-Sec61␤.…”

Section: The Mitotic Er Is Composed Primarily Of Extended Cisternaesupporting

confidence: 49%

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Cisternal Organization of the Endoplasmic Reticulum during Mitosis

Lü

Ladinsky

Kirchhausen

2009

MBoC

189

211

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The endoplasmic reticulum (ER) of animal cells is a single, dynamic, and continuous membrane network of interconnected cisternae and tubules spread out throughout the cytosol in direct contact with the nuclear envelope. During mitosis, the nuclear envelope undergoes a major rearrangement, as it rapidly partitions its membrane-bound contents into the ER. It is therefore of great interest to determine whether any major transformation in the architecture of the ER also occurs during cell division. We present structural evidence, from rapid, live-cell, three-dimensional imaging with confirmation from high-resolution electron microscopy tomography of samples preserved by high-pressure freezing and freeze substitution, unambiguously showing that from prometaphase to telophase of mammalian cells, most of the ER is organized as extended cisternae, with a very small fraction remaining organized as tubules. In contrast, during interphase, the ER displays the familiar reticular network of convolved cisternae linked to tubules.

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Section: The Mitotic Er Is Composed Primarily Of Extended Cisternaesupporting

confidence: 49%

“…Members of the reticulon and DP1/Yop1p ER-protein families are thought to tubulate ER membranes Hu et al, 2008;Shibata et al, 2008). It is therefore possible that during mitosis, transient loss of their proposed tubulation function might facilitate the acute loss of tubular ER that we report.…”

Section: Discussionmentioning

confidence: 72%

Cisternal Organization of the Endoplasmic Reticulum during Mitosis

Lü

Ladinsky

Kirchhausen

2009

MBoC

189

211

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“…Moreover, it has been demonstrated that the yeast RTN Rtn1p is sufficient to induce tubule formation in vitro when mixed with lipids [11]. Furthermore, similar results from Hu et al have previously been obtained for RTN4A where its ability to form ER tubule structures was demonstrated in association with DP1, an integral membrane protein orthologues of yeast Rtn1p-binding protein Yop1 [12].…”

Section: Introductionsupporting

confidence: 71%

The reticulons: Guardians of the structure and function of the endoplasmic reticulum

Sano

Bernardoni

Piacentini

2012

Experimental Cell Research

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The endoplasmic reticulum (ER) consists of the nuclear envelope and a peripheral network of tubules and membrane sheets. The tubules are shaped by a specific class of curvature stabilizing proteins, the reticulons and DP1; however it is still unclear how the sheets are assembled. The ER is the cellular compartment responsible for secretory and membrane protein synthesis. The reducing conditions of ER lead to the intra/inter-chain formation of new disulphide bonds into polypeptides during protein folding assessed by enzymatic or spontaneous reactions. Moreover, ER represents the main intracellular calcium storage site and it plays an important role in calcium signaling that impacts many cellular processes. Accordingly, the maintenance of ER function represents an essential condition for the cell, and ER morphology constitutes an important prerogative of it. Furthermore, it is well known that ER undergoes prominent shape transitions during events such as cell division and differentiation. Thus, maintaining the correct ER structure is an essential feature for cellular physiology. Now, it is known that proper ER-associated proteins play a fundamental role in ER tubules formation. Among these ER-shaping proteins are the reticulons (RTN), which are acquiring a relevant position. In fact, beyond the structural role of reticulons, in very recent years new and deeper functional implications of these proteins are emerging in relation to their involvement in several cellular processes.

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“…REEP members such as REEP5, a member of the DP1 family, regulate intracellular trafficking by affecting ER membrane structure and cargo capacity and by acting as adapter proteins 12. Contrasting findings regarding the intracellular localization and mechanisms of action of the REEP proteins have been described 20, 21.…”

Section: Discussionmentioning

confidence: 99%

REEP5 (Receptor Accessory Protein 5) Acts as a Sarcoplasmic Reticulum Membrane Sculptor to Modulate Cardiac Function

Yao

Xie

et al. 2018

JAHA

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BackgroundHeart failure is a complex syndrome characterized by cardiac contractile impairment with high mortality. Defective intracellular Ca2+ homeostasis is the central cause under this scenario and tightly links to ultrastructural rearrangements of sarcolemmal transverse tubules and the sarcoplasmic reticulum (SR); however, the modulators of the SR architecture remain unknown. The SR has been thought to be a specialized endoplasmic reticulum membrane system. Receptor accessory proteins (REEPs)/DP1/Yop1p are responsible for shaping high‐curvature endoplasmic reticulum tubules. This study aimed to determine the role of REEPs in SR membrane shaping and thus cardiac function.Methods and ResultsWe identified REEP5 (receptor accessory protein 5) as more highly expressed than other REEP members in adult rat ventricular myocardium, and it was downregulated in the failing hearts. Targeted inactivation of REEP5 in rats specially deformed the cardiac SR membrane without affecting transverse tubules, and this was visualized by focused ion beam scanning electron microscopy–based 3‐dimensional reconstruction. Accordingly, simultaneous recordings of depolarization‐induced Ca2+ currents and Ca2+ transients in REEP5‐null cardiomyocytes revealed normal L‐type Ca2+ channel currents but a depressed SR Ca2+ release. Consequently, the excitation–contraction coupling gain of cardiomyocytes and consequent cardiac contractility were compromised. REEP5 deficiency did not alter the expression of major proteins involved in Ca2+ handling in the heart.Conclusions REEP5 modulates cardiac function by shaping the SR. REEP5 defect deforms the SR architecture to depress cardiac contractility. REEP5‐dependent SR shaping might have potential as a therapeutic target for heart failure.

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Membrane Proteins of the Endoplasmic Reticulum Induce High-Curvature Tubules

Cited by 393 publications

References 23 publications

Cisternal Organization of the Endoplasmic Reticulum during Mitosis

Cisternal Organization of the Endoplasmic Reticulum during Mitosis

The reticulons: Guardians of the structure and function of the endoplasmic reticulum

REEP5 (Receptor Accessory Protein 5) Acts as a Sarcoplasmic Reticulum Membrane Sculptor to Modulate Cardiac Function

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