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Gorrell L, Omari S, Makareeva E, et al. Noncanonical ER-Golgi trafficking and autophagy of endogenous procollagen in osteoblasts. Cell Mol Life Sci. 2021;78(24):8283-8300doi: 10.1007/s00018-021-04017-z.
Gorrell, L., Omari, S., Makareeva, E., & Leikin, S. (2021). Noncanonical ER-Golgi trafficking and autophagy of endogenous procollagen in osteoblasts. Cellular and molecular life sciences : CMLS, 78(24), 8283-8300. https://doi.org/10.1007/s00018-021-04017-z
Gorrell, Laura, et al. "Noncanonical ER-Golgi trafficking and autophagy of endogenous procollagen in osteoblasts." Cellular and molecular life sciences : CMLS vol. 78,24 (2021): 8283-8300. doi: https://doi.org/10.1007/s00018-021-04017-z
Gorrell L, Omari S, Makareeva E, Leikin S. Noncanonical ER-Golgi trafficking and autophagy of endogenous procollagen in osteoblasts. Cell Mol Life Sci. 2021 Dec;78(24):8283-8300. doi: 10.1007/s00018-021-04017-z. Epub 2021 Nov 15. PMID: 34779895.
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Cell Mol Life Sci. 2021 Dec;78(24):8283-8300. doi: 10.1007/s00018-021-04017-z. Epub 2021 Nov 15.

Noncanonical ER-Golgi trafficking and autophagy of endogenous procollagen in osteoblasts.

Cellular and molecular life sciences : CMLS

Laura Gorrell, Shakib Omari, Elena Makareeva, Sergey Leikin

Affiliations

  1. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD, 20892, USA.
  2. Rensselaer Polytechnic Institute, Troy, NY, 12180, USA.
  3. Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA.
  4. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD, 20892, USA. [email protected].

PMID: 34779895 DOI: 10.1007/s00018-021-04017-z

Abstract

Secretion and quality control of large extracellular matrix proteins remain poorly understood and debated, particularly transport intermediates delivering folded proteins from the ER to Golgi and misfolded ones to lysosomes. Discrepancies between different studies are related to utilization of exogenous cargo, off-target effects of experimental conditions and cell manipulation, and identification of transport intermediates without tracing their origin and destination. To address these issues, here we imaged secretory and degradative trafficking of type I procollagen in live MC3T3 osteoblasts by replacing a region encoding N-propeptide in endogenous Col1a2 gDNA with GFP cDNA. We selected clones that produced the resulting fluorescent procollagen yet had normal expression of key osteoblast and ER/cell stress genes, normal procollagen folding, and normal deposition and mineralization of extracellular matrix. Live-cell imaging of these clones revealed ARF1-dependent transport intermediates, which had no COPII coat and delivered procollagen from ER exit sites (ERESs) to Golgi without stopping at ER-Golgi intermediate compartment (ERGIC). It also confirmed ERES microautophagy, i.e., lysosomes engulfing ERESs containing misfolded procollagen. Beyond validating these trafficking models for endogenous procollagen, we uncovered a probable cause of noncanonical cell stress response to procollagen misfolding. Recognized and retained only at ERESs, misfolded procollagen does not directly activate the canonical UPR, yet it disrupts the ER lumen by blocking normal secretory export from the ER.

© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

Keywords: Autophagy; Collagen; Live-cell imaging; Quality control; Trafficking

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