CREB3L1-mediated functional and structural adaptation of the secretory pathway in hormone-stimulated thyroid cells

J Cell Sci. 2017 Dec 15;130(24):4155-4167. doi: 10.1242/jcs.211102. Epub 2017 Nov 1.

Abstract

Many secretory cells increase the synthesis and secretion of cargo proteins in response to specific stimuli. How cells couple increased cargo load with a coordinate rise in secretory capacity to ensure efficient transport is not well understood. We used thyroid cells stimulated with thyrotropin (TSH) to demonstrate a coordinate increase in the production of thyroid-specific cargo proteins and ER-Golgi transport factors, and a parallel expansion of the Golgi complex. TSH also increased expression of the CREB3L1 transcription factor, which alone caused amplified transport factor levels and Golgi enlargement. Furthermore, CREB3L1 potentiated the TSH-induced increase in Golgi volume. A dominant-negative CREB3L1 construct hampered the ability of TSH to induce Golgi expansion, implying that this transcription factor contributes to Golgi expansion. Our findings support a model in which CREB3L1 acts as a downstream effector of TSH to regulate the expression of cargo proteins, and simultaneously increases the synthesis of transport factors and the expansion of the Golgi to synchronize the rise in cargo load with the amplified capacity of the secretory pathway.

Keywords: CREB3L1; FRTL-5; Golgi; Membrane traffic; Secretory pathway; TSH.

MeSH terms

  • Cell Line
  • Cyclic AMP Response Element-Binding Protein / genetics*
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Endoplasmic Reticulum / genetics
  • Endoplasmic Reticulum / metabolism
  • Gene Expression Regulation / genetics
  • Golgi Apparatus / genetics*
  • Golgi Apparatus / metabolism
  • Humans
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Secretory Pathway / genetics
  • Thyroid Gland / metabolism*
  • Thyrotropin / genetics*
  • Thyrotropin / metabolism

Substances

  • CREB3L1 protein, human
  • Cyclic AMP Response Element-Binding Protein
  • Nerve Tissue Proteins
  • Thyrotropin