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Steven Cala, Ph.D.
Associate Professor & Graduate Officer

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Contact Information

Wayne State University
4235 Scott Hall

540 East Canfield
Detroit, MI 48201

Phone:  313-577-8734
FAX:    313-577-8615



B.S. in Chemistry - Purdue University

M.S. in Chemistry - Texas A&M University

Ph.D. in Pharmacology - Indiana University

Research Interests

Function-based analysis of the cardiac endoplasmic and sarcoplasmic reticulum proteome (Present at 61st annual meeting of the Biophysical Society 2017)


Our laboratory’s research is focused on the physiology of the adult cardiomyocyte, and the structure of the sarcoplasmic reticulum. Our studies involve proteins that regulate release of calcium from the sarcoplasmic reticulum for contraction.  One of these proteins, calsequestrin, is a possible calcium sensor that helps control the amount of calcium released at each depolarization.  Other proteins of interest include two homologous proteins, triadin and junctin, that carry the signal from calsequestrin to the SR Ca2+-release channel.  We’re investigating biochemical processes that regulate the biosynthesis and interactions of these proteins; trying to understand how these protein complexes form in heart cells; and how their functions may be altered in disease.


Calsequestrin-2 (CSQ 2) contains sites on its C-terminus that are efficient substrates for protein kinase CK2 in vivo.  Phosphorylation of these sites occurs to a high degree in the intact heart. The reaction is a novel biochemical reaction mechanism that acts from the cytoplasmic CK2 to the SR lumen by acting on CSQ2 while it is undergoing translocation into the rough ER lumen.

CK2 phosphorylation sites in CSQ2: CSQ2 and CSQ1 are about 60% identical, and exhibit a conserved glycosylation site N316.  Part of the CSQ2-specific tail is shown for several species, and contains CK2-sensitive serine residues (yellow highlighted in shaded box). Adult rat heart cells were treated or not treated for 48 h with CSQ2-adenovirus (MOI=100). Detergent (0.1% Triton X-100) was added, and mixtures (~80 μg) incubated 10 min in 10 μm [λ-32P]ATP-containing buffer, to produce this autoradiogram.

Model of trans-compartment CSQ2 phosphorylation, occurring by a cytosolic CK2 while CSQ2 is undergoing ER translocation.  Evidence suggests that CK2 phosphorylation leads to CSQ2 retention in rough ER.

In heart failure tissue, the state of CSQ2 phosphorylation is increased, and the level of CSQ2 in perinuclear rough is dramatically increased.  This reaction has significant potential as a mechanism of biochemical change in the SR, possibly impacting Ca homeostasis. This may be a crucial event in hear and may explain, in part, the altered contractile properties of the heart that develops during failure.

Mass spectra of CSQ2 from C and HF dog hearts  CSQ2 purified from canine left ventricular samples was analyzed by mass spectrometry to reveal its polymorphic structure.  Individual spectra contained mass peaks corresponding to changes in either one phosphate (multiples of 81 Da), or one mannose (multiples of 162 Da). Mass peak heights at every 81 kDa were determined and plotted as a percentage of the total (%CSQ molecules). FIve C hearts (green peaks), 3 HFi hearts (red peaks), and 4 HFt hearts (blue, 4 left ventricle posterior wall samples; lavender, 3 left ventricle septal wall samples from same dogs). Shaded area on right (rough ER) designates CSQ forms with mass corresponding to as little as a single step of mannose trimming (Man9,8, peak B), whereas further trimming of CSQ is found in muscle only (peak A).  The presumed mass of CSQ just after biosynthesis and folding (mass = 47,478 Da; Man9 with 3 phosphates) is indicated by an asterisk (*).


Recent Publications

  1. Wu AZ, Xu D, Yang N, Lin SF, Chen PS, Cala SE, Chen Z  Phospholamban is concentrated in the nuclear envelope of cardiomyocytes and involved in perinuclear/nuclear calcium handling. J Mol Cell Cardiol. 2016 Sep 15. pii: S0022-2828(16)30357-1. PMID: 27642167

  2. Sleiman, N.H., McFarland, T.P., Jones, L.R. and Cala, S.E., Transitions of protein traffic from cardiac ER to junctional SR., J Mol Cell Cardiol. 2015 Jan 29;81C:34-45. PMID: 25640161

  3. Jacob S, Sleiman NH, Kern S, Jones LR, Sala-Mercado JA, McFarland TP, Sabbah HH, Cala S.: Altered calsequestrin glycan processing is common to diverse models of canine heart failure. Mol Cell Biochem. 377, 11-21, 2013. PMID: 23456435.

  4. Kern, S., Feng, H.-Z., Wei, H., Cala, S., Jin, J.-P: Up-regulation of Alpha-Smooth Muscle Actin in Cardiomyocytes from Expressing N-terminal Truncated Cardiac Troponin I Non-hypertrophic and Non-Failing Transgenic Mouse Hearts, FEBS Open Bio, 4:11-17, 2013. PMID: 24319652

  5. Guo, A., Cala, S. (co-corresponding author), Song, L.-S.: Calsequestrin accumulation in rough endoplasmic reticulum promotes perinuclear Ca2+ release. J. Biol. Chem. 287, 16670-80, 2012. PMID:22457350

  6. McFarland, T., Sleiman, N., Yaeger, D., Cala.S.: Identification of cardiac calsequestrin kinase as the cytosolic protein kinase CK2, Mol. Cell. Biochem. 353, 81-91, 2011. PMID: 21431367

  7. McFarland, T., Milstein, M., Cala, S.: Rough endoplasmic reticulum to junctional sarcoplasmic reticulum trafficking of calsequestrin in adult cardiomyocytes, J. Mol. Cell. Card. 49, 556-64, 2010. PMID:2059500.


A complete list of Dr. Cala's publications can be found at PubMed-Cala

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This site was created and is maintained by: Christine Cupps
 Updated: 02/13/2017