A Substrate Preference for the Rough Endoplasmic Reticulum Resident Protein FKBP22 during Collagen Biosynthesis

Ishikawa, Yoshihiro; Bächinger, Hans Peter

doi:10.1074/jbc.m114.561944

Cited by 40 publications

(68 citation statements)

References 66 publications

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“…The binding affinity between the SH3 domain and Hsp47 (K d = 0.26 ± 0.09 μM; Fig. 3B) is comparable to that between collagen and Hsp47 (K d = 0.2∼4 μM) (20,21). This indicates that these three molecules (i.e., collagen-Hsp47-SH3 domain) likely form an equilibrium complex at the rER exit site.…”

Section: Discussionmentioning

confidence: 68%

“…The SH3 domain was injected as analyte over the surface of chips, each containing one of eight different types of collagen (type I, II, III, IV, V, VI, X, or XI collagens). Hsp47 was previously shown to bind to native type I, II, III, IV, V, VI, and X collagen by this method (20,21), and was used as a positive control.…”

Section: Resultsmentioning

confidence: 99%

“…Hsp47 and FKBP65 were purified from 17-d-old chicken embryos with the methods described previously (51,52). Human recombinant FKBP22 was purified from E. coli by methods described previously (20).…”

Section: Methodsmentioning

confidence: 99%

“…Isolation and purification of bovine type I, II, III, and V were described previously (20). Mouse type IV collagen and human recombinant type X collagen were purified as described by using HR9 and 293 cells, respectively (53,54).…”

Section: Methodsmentioning

confidence: 99%

“…We expected that fibrillin-1 might share the same molecular sorting mechanism with collagens because of its interaction with Hsp47 (K d = 0.33 ± 0.06 μM; Fig. 4F) showing similar binding affinity as collagen-Hsp47 (K d = 0.2 ∼4 μM) (20,21). However, fibrillin-1 was secreted normally into the medium of Hsp47 −/− MEFs (Fig.…”

Section: How Large Ecm Molecules Are Sorted Into Special Copii Transportmentioning

confidence: 99%

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Intracellular mechanisms of molecular recognition and sorting for transport of large extracellular matrix molecules

Ishikawa

Ito

Nagata

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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104

118

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Extracellular matrix (ECM) proteins are biosynthesized in the rough endoplasmic reticulum (rER) and transported via the Golgi apparatus to the extracellular space. The coat protein complex II (COPII) transport vesicles are approximately 60-90 nm in diameter. However, several ECM molecules are much larger, up to several hundreds of nanometers. Therefore, special COPII vesicles are required to coat and transport these molecules. Transmembrane Protein Transport and Golgi Organization 1 (TANGO1) facilitates loading of collagens into special vesicles. The Src homology 3 (SH3) domain of TANGO1 was proposed to recognize collagen molecules, but how the SH3 domain recognizes various types of collagen is not understood. Moreover, how are large noncollagenous ECM molecules transported from the rER to the Golgi? Here we identify heat shock protein (Hsp) 47 as a guide molecule directing collagens to special vesicles by interacting with the SH3 domain of TANGO1. We also consider whether the collagen secretory model applies to other large ECM molecules.E xtracellular matrix (ECM) proteins are the most abundant proteins in our body. They build the body architecture and help to maintain tissue homeostasis in bone, skin, cartilage, and tendon (1). They are biosynthesized in the rough endoplasmic reticulum (ER; rER) and traverse the Golgi apparatus en route to the extracellular space. A transport vesicle for cargo exists to traffic molecules from the rER into the extracellular space. This secretory vesicle is called a coat protein complex II (COPII) vesicle (2-4). It is generated at the ER exit site and usually has a diameter of 60-90 nm. This carrier can transport many secreted proteins. However, larger or elongated molecules, especially collagens and other ECM molecules, will not fit into such small vesicles.There are more than 20 different collagen types in humans (5, 6). Type I, II, III, and V collagens are classified as fibrillar collagens, which are the most abundant. Type IV collagen is an important structural element in basement membranes. Type VII collagen forms anchoring fibrils at the epidermal-dermal junction in skin. These collagens are all more than 300 nm long. In addition to its elongated triple helical structure, type VII collagen has a 140-kDa noncollagenous domain at the amino terminus. Although more flexible than collagens, fibrillin molecules are also elongated, measured to be approximately 150 nm in length (7). For these molecules, special COPII vesicles or other trafficking systems are required for secretion.It has been proposed that procollagen molecules, which are the precursors of collagen, are transferred in COPII vesicles to the Golgi (8-10). In 2009, Transmembrane Protein Transport and Golgi Organization 1 (TANGO1), encoded by MIA3, was shown to facilitate collagens into COPII vesicles at the ER exit site (11). In the cytoplasm, TANGO1 interacts with Sec23A/Sec24C, the outer molecules of COPII vesicles, and cTAGE5, a homolog of TANGO1 that lacks the rER domains of TANGO. These interactions occur via a ...

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Section: Discussionmentioning

confidence: 68%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: How Large Ecm Molecules Are Sorted Into Special Copii Transportmentioning

confidence: 99%

See 3 more Smart Citations

Intracellular mechanisms of molecular recognition and sorting for transport of large extracellular matrix molecules

Ishikawa

Ito

Nagata

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

104

118

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The Ehlers–Danlos syndromes, rare types

Brady¹,

Demirdas²,

Fournel‐Gigleux³

et al. 2017

American J of Med Genetics Pt C

181

288

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The Ehlers–Danlos syndromes comprise a clinically and genetically heterogeneous group of heritable connective tissue disorders, which are characterized by joint hypermobility, skin hyperextensibility, and tissue friability. In the Villefranche Nosology, six subtypes were recognized: The classical, hypermobile, vascular, kyphoscoliotic, arthrochalasis, and dermatosparaxis subtypes of EDS. Except for the hypermobile subtype, defects had been identified in fibrillar collagens or in collagen‐modifying enzymes. Since 1997, a whole spectrum of novel, clinically overlapping, rare EDS‐variants have been delineated and genetic defects have been identified in an array of other extracellular matrix genes. Advances in molecular testing have made it possible to now identify the causative mutation for many patients presenting these phenotypes. The aim of this literature review is to summarize the current knowledge on the rare EDS subtypes and highlight areas for future research. © 2017 Wiley Periodicals, Inc.

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Kyphoscoliotic Ehlers‐Danlos syndrome caused by pathogenic variants in FKBP14 : Further insights into the phenotypic spectrum and pathogenic mechanisms

et al. 2022

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The Ehlers-Danlos syndromes (EDS) are a heterogeneous group of heritable connective tissue diseases. The autosomal recessive kyphoscoliotic EDS results from deficiency of either lysyl hydroxylase 1 (encoded by PLOD1), crucial for collagen cross-linking; or the peptidyl-prolyl cis-trans isomerase family FK506binding protein 22 kDa (FKBP22 encoded by FKBP14), a molecular chaperone of types III, IV, VI, and X collagen. This study reports the clinical manifestations of three probands with homozygous pathogenic FKBP14 variants, including the previously reported c.362dupC; p.(Glu122Argfs*7) variant, a novel missense variant (c.587A>G; p.(Asp196Gly)) and a start codon variant (c.2T>G; p.?). Consistent clinical features in the hitherto reported individuals (n = 40) are kyphoscoliosis, generalized joint hypermobility and congenital muscle hypotonia. Severe vascular complications have been observed in 12.5%. A previously unreported feature is microcornea observed in two probands reported here. Both the c.587A>G and the c.362dupC variant cause complete loss of FKBP22. With immunocytochemistry on dermal fibroblasts, we provide the first evidence for intracellular retention of types III and VI collagen in EDS-FKBP14. Scratch wound assays were largely normal. Western blot of proteins involved in the unfolded protein response and autophagy did not reveal significant upregulation in dermal fibroblasts.

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A Substrate Preference for the Rough Endoplasmic Reticulum Resident Protein FKBP22 during Collagen Biosynthesis

Cited by 40 publications

References 66 publications

Intracellular mechanisms of molecular recognition and sorting for transport of large extracellular matrix molecules

Intracellular mechanisms of molecular recognition and sorting for transport of large extracellular matrix molecules

The Ehlers–Danlos syndromes, rare types

Kyphoscoliotic Ehlers‐Danlos syndrome caused by pathogenic variants in FKBP14 : Further insights into the phenotypic spectrum and pathogenic mechanisms

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