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. 2019 Sep-Oct:42:15-20.
doi: 10.1016/j.carpath.2019.05.001. Epub 2019 May 24.

An expanded proteome of cardiac t-tubules

Jenice X Cheah  1 , Tim O Nieuwenhuis  1 , Marc K Halushka  2
Affiliations

An expanded proteome of cardiac t-tubules

Jenice X Cheah et al. Cardiovasc Pathol. 2019 Sep-Oct.

Abstract

Background: Transverse tubules (t-tubules) are important structural elements, derived from sarcolemma, found on all striated myocytes. These specialized organelles create a scaffold for many proteins crucial to the effective propagation of signal in cardiac excitation-contraction coupling. The full protein composition of this region is unknown.

Methods: We characterized the t-tubule subproteome using 52,033 immunohistochemical images covering 13,203 proteins from the Human Protein Atlas (HPA) cardiac tissue microarrays. We used HPASubC, a suite of Python tools, to rapidly review and classify each image for a specific t-tubule staining pattern. The tools Gene Cards, String 11, and Gene Ontology Consortium as well as literature searches were used to understand pathways and relationships between the proteins.

Results: There were 96 likely t-tubule proteins identified by HPASubC. Of these, 12 were matrisome proteins and 3 were mitochondrial proteins. A separate literature search identified 50 known t-tubule proteins. A comparison of the 2 lists revealed only 17 proteins in common, including 8 of the matrisome proteins. String11 revealed that 94 of 127 combined t-tubule proteins generated a single interconnected network.

Conclusion: Using HPASubC and the HPA, we identified 78 novel, putative t-tubule proteins and validated 17 within the literature. This expands and improves our knowledge of this important subcellular structure of the cardiac myocyte. This information can be used to identify new structural targets involved in excitation-contraction coupling that may be altered in disease.

Keywords: Caveolin; Proteomics; T-tubule.

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Conflict of interest statement

Conflict of interest

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Caveolin patterns of t-tubule staining. These patterns are representative of the patterns seen across all of the reported proteins. Images from the Human Protein Atlas.
Fig. 2.
Fig. 2.
Representative matrisome protein expression at the t-tubule. Key: ANXA6: Annexin 6, COL4A1: Collagen type IV alpha 1 chain; LAMB1: laminin subunit beta 1; ADIPOQ: adiponectin, C1Q and collagen domain containing; VCAN: versican; COL6A2: Collagen type VI alpha 2 chain. Images from the Human Protein Atlas.
Fig. 3.
Fig. 3.
The entire t-tubule interactome map (String 11). Red boxes indicate t-tubule proteins new to this study.
See this image and copyright information in PMC

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