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Molecular and Cellular Biochemistry

, Volume 457, Issue 1–2, pp 201–214 | Cite as

Adiponectin secretion from cardiomyocytes produces canonical multimers and partial co-localization with calsequestrin in junctional SR

  • Joanna Solarewicz
  • Amanda Manly
  • Stephanie Kokoszka
  • Naama Sleiman
  • Todd Leff
  • Steven CalaEmail author
Article
  • 109 Downloads

Abstract

Adiponectin (ADN) is an abundant protein in serum, secreted by adipocytes, that acts as a signal for fat metabolism. It is marked by a complex molecular structure that results from processes within the secretory pathway, producing a canonical set of multimers. ADN may also be secreted from cardiomyocytes, where a unique sarcomeric endoplasmic/sarcoplasmic reticulum (ER/SR) substructure has been characterized primarily for its Ca handling. We expressed ADN in cultured primary adult cardiomyocytes and nonmuscle (COS) cells. After 48 h of ADN expression by adenovirus treatment, roughly half of synthesized ADN was secreted from cardiomyocytes, and half was still in-transit within inner membrane compartments, similar to COS cells. Cardiomyocytes and COS cells both produced ADN in the three canonical forms: trimers, hexamers, and 18-mers. Higher rates of secretion occurred for higher-molecular weight multimers, especially 18-mers. The highest levels of ADN protein, whether in transit or secreted, were present as trimers and hexamers. In nonmuscle cell lines, ADN trafficked through ER and Golgi compartments as expected. In contrast, ADN in primary adult cardiomyocytes populated ER/SR tubules along the edges of sarcomeres that emanated from nuclear surfaces. Prominent co-localization of ADN occurred with calsequestrin, a marker of junctional SR, the Ca2+-release compartment of the cell. The early steps in ADN trafficking re-trace those recently described for newly made junctional SR proteins, involving a nuclear envelope (NE) translocation into SR tubules that are oriented along sarcolemmal transverse (T)-tubules (NEST pathway).

Keywords

Adiponectin Calsequestrin Trafficking Cardiomyocyte Junctional SR NEST 

Abbreviations

ER

Endoplasmic reticulum

jSR

Junctional sarcoplasmic reticulum

ADN

Adiponectin

MOI

Multiplicity of infection

Pfu

Plaque-forming units

HMW

High molecular weight

MMW

Medium molecular weight

LMW

Low molecular weight

ADN-WT

Wild-type (human) adiponectin

ADN-Flag

Flag-tagged adiponectin

native-PAGE

Native polyacrylamide gel electrophoresis

BFA

Brefeldin A

NEST pathway

Nuclear envelope to SR along T-tubules pathway

z-tubules

SR tubules that traffic newly made proteins roughly aligned with the sarcomeric z-line and T-tubules

Notes

Acknowledgements

This work was supported by an Incubator Grant 1-77311 from the Office of Vice President for Research, Wayne State University.

Compliance with ethical standards

Conflict of interest

The authors do not have any conflicts of interest to declare.

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PhysiologyWayne State UniversityDetroitUSA
  2. 2.Department of PathologyWayne State UniversityDetroitUSA

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