1,721,086 research outputs found
Formation, isomerization and reduction of disulphide bonds during protein quality control in the endoplasmic reticulum.
No full text
From antibodies to adiponectin: role of ERp44 in sizing and shaping protein secretion
No full textA large fraction of the proteome is synthesized and folded in the endoplasmic reticulum (ER), a multifunctional compartment also playing pivotal
roles in Ca2+ storage, redox homeostasis and signalling. From the ER, secretory proteins begin their journey towards their final destinations, the
organelles of the exocytic and endocytic compartments, the plasma membrane or the extracellular space. Fidelity of protein-based intracellular
communication is guaranteed by quality control (QC) mechanisms located at the ER–Golgi interface, which restrict forward transport to native
proteins. QC is used also to time or shape the secretome. Furthermore, professional secretory cells face a problem of quantity, as well as quality
of their protein products. This essay summarizes recent findings that identify ERp44 as a key regulator of protein secretion, Ca2+ signalling and
redox regulation
Selective Secretion of KDEL-Bearing Proteins: Mechanisms and Functions
No full textIn multicellular organisms, cells must continuously exchange messages with the right meaning, intensity, and duration. Most of these messages are delivered through cognate interactions between membrane and secretory proteins. Their conformational maturation is assisted by a vast array of chaperones and enzymes, ensuring the fidelity of intercellular communication. These folding assistants reside in the early secretory compartment (ESC), a functional unit that encompasses endoplasmic reticulum (ER), intermediate compartment and cis-Golgi. Most soluble ESC residents have C-terminal KDEL-like motifs that prevent their transport beyond the Golgi. However, some accumulate in the ER, while others in downstream stations, implying different recycling rates. Moreover, it is now clear that cells can actively secrete certain ESC residents but not others. This essay discusses the physiology of their differential intracellular distribution, and the mechanisms that may ensure selectivity of release
ERp44 and ERGIC-53 Synergize in Coupling Efficiency and Fidelity of IgM Polymerization and Secretion
No full textOwing to the quality control mechanisms operating in
the early secretory compartment, only native proteins
are secreted. Despite the difficulties in assembling
planar immunoglobulin M (IgM) polymers, antibodysecreting
cells can release up to thousands of IgM
per second. The finding that secretory μ (μs) chains
bind to ERGIC-53, a lectin transporter that cycles in the
early secretory compartment, suggested that ERGIC-53
hexamers could provide a polymerization platform. Here,
we show that ERGIC-53 binds to the conserved Asn563
glycan in the C-terminal μs tailpiece (μstp). Removal
of this glycan inhibits ERGIC-53 binding and results
in the rapid formation of larger polymeric assemblies.
In contrast, removal of the Asn402 oligosaccharides
prevents both polymerization and secretion. ERp44,
a chaperone that interacts with ERGIC-53, binds to
Cys575 in the μstp, providing a fail-safe mechanism
that retrieves unpolymerized IgM subunits and promotes
polymerization. The coordinated action of ERGIC-53 and
ERp44 provides a way to improve the efficiency of IgM
secretion without perturbing its fidelity
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