Beaded filaments and long-spacing fibrils: Relation to type VI collagen

doi:10.1016/S0022-5320(84)80010-6

Journal of Ultrastructure Research

Volume 89, Issue 2, November 1984, Pages 136-145

https://doi.org/10.1016/S0022-5320(84)80010-6 Get rights and content

“Beaded filaments” have been found in fibroblast cultures prepared from chicken embryo leg tendons and cornea and from the dermis of human skin. With negative staining, they appear as single, unbranched, flexible strands ∼3 nm in width and up to at least 2 itμm in length. Pairs of “beads” are distributed on the filament at regular intervals of 110 nm. The beaded filaments appear to be resistant to the action of trypsin and bacterial collagenase. The filaments also occur in bundles with beads laterally aligned to form long-spacing-type fibrils, which appear to be identical with many fibrous-long-spacing-type fibrils described, but not identified, by others in a variety of normal and pathological tissues. The long-spacing fibrils are numerous at several sites of active collagen fibrillogenesis. Comparison of the beaded filament structure with molecular models for various collagens described in the literature suggests that they are a filamentous form of type VI collagen.

References (72)

BoguschG.
J. Mol. Cell. Cardiol.
(1975)
BrunsR.R. et al.
Exp. Cell Res.
(1980)
CraviotoH. et al.
J. Ultrastruct. Res.
(1968)
DehmP. et al.
Biochim. Biophys. Acta
(1971)
DoyleB.B. et al.
J. Mol. Biol.
(1975)
EngelJ. et al.
J. Mol. Biol.
(1981)
GeislerN. et al.
Cell
(1982)
GoldbergB.
Cell
(1979)
GrangerB.L. et al.
Cell
(1982)
GreenH. et al.
Cell
(1974)

HashimotoK. et al.

J. Invest. Dermatol.

(1974)

HendersonD. et al.

J. Mol. Biol.

(1982)

HessleH. et al.

J. Biol. Chem.

(1984)

NakaoK. et al.

Exp. Mol. Pathol.

(1972)

SilberbergR. et al.

J. Ultrastruct. Res.

(1970)

SunC.N. et al.

Tissue Cell

(1975)

TruebB. et al.

J. Biol. Chem.

(1984)

AebiU. et al.

J. Cell Biol.

(1983)

BanfieldW.G. et al.

Arch. Pathol.

(1973)

BentzH. et al.

BrunsR.R.

J. Cell Biol.

(1969)

BuckwalterJ.A. et al.

Clin. Orthopaedics Rel. Res.

(1979)

ChapmanJ.A. et al.

Connect. Tissue Res.

(1972)

ChatterjeeP.

J. Anat.

(1973)

CornahM.S. et al.

J. Anat.

(1970)

DryllA. et al.

Virchows Arch. Pathol. Anat.

(1981)

EdwardsR.P.

Brit. J. Dermatol.

(1975)

FahrenbachW.H. et al.

Anat. Rec.

(1966)

FredericksonR.G. et al.

Amer. J. Anat.

(1977)

FurthmayrH. et al.

Biochem. J.

(1983)

GoldbergB. et al.

J. Cell Biol.

(1964)

GrossJ.

J. Biophys. Biochem. Cytol.

(1956)

GrossJ. et al.

HayesR.L. et al.

J. Cell Sci.

(1967)

HildingD.A. et al.

Laryngoscope

(1964)

HuxleyH.E.

J. Mol. Biol.

(1963)

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: The work was supported by National Institutes of Health Research Grant AM3564.

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Beaded filaments and long-spacing fibrils: Relation to type VI collagen

J. Mol. Cell. Cardiol.

Exp. Cell Res.

J. Ultrastruct. Res.

Biochim. Biophys. Acta

J. Mol. Biol.

J. Mol. Biol.

Cell

Cell

Cell

Cell

J. Invest. Dermatol.

J. Mol. Biol.

J. Biol. Chem.

Exp. Mol. Pathol.

J. Ultrastruct. Res.

Tissue Cell

J. Biol. Chem.

J. Cell Biol.

Arch. Pathol.

J. Cell Biol.

Clin. Orthopaedics Rel. Res.

Connect. Tissue Res.

J. Anat.

J. Anat.

Virchows Arch. Pathol. Anat.

Brit. J. Dermatol.

Anat. Rec.

Amer. J. Anat.

Biochem. J.

J. Cell Biol.

J. Biophys. Biochem. Cytol.

J. Cell Sci.

Laryngoscope

J. Mol. Biol.