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Proc Natl Acad Sci U S A. 2016 Oct 11;113(41):E6036-E6044. Epub 2016 Sep 27.

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

Author information

1
Research Department, Shriners Hospital for Children, Portland, OR 97239; Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, OR 97239.
2
Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kyoto 603-8555, Japan.
3
Research Department, Shriners Hospital for Children, Portland, OR 97239; Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, OR 97239; hpb@shcc.org.

Abstract

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.

KEYWORDS:

COPII vesicles; Hsp47; TANGO1; collagen; secretion

PMID:
27679847
PMCID:
PMC5068301
DOI:
10.1073/pnas.1609571113
[Indexed for MEDLINE]
Free PMC Article

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