Microtubule-associated protein-4 (MAP-4) inhibits microtubule-dependent distribution of mRNA in isolated neonatal cardiocytes

doi:10.1016/j.cardiores.2006.04.001

Cardiovascular Research 2006 71(3):506-516; doi:10.1016/j.cardiores.2006.04.001

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Microtubule-associated protein-4 (MAP-4) inhibits microtubule-dependent distribution of mRNA in isolated neonatal cardiocytes

Dimitri Scholz^a^,c^,*, Paul McDermott^a^,c, Maria Garnovskaya^b^,c, Thomas N. Gallien^a^,c, Stefan Huettelmaier^d, Christina DeRienzo^a^,c and George Cooper, IV^a^,c

^aGazes Cardiac Research Institute, Cardiology Division, Medical University of South Carolina, United States
^bMedical and Research Services of the Ralph H. Johnson Veteran Affairs Medical Center, Nephrology Division, Medical University of South Carolina, United States
^cDepartment of Veterans Affairs Medical Center, Charleston, SC 29401, United States
^dDepartment of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461, United States

^* Corresponding author. Gazes Cardiac Research Institute, Medical University of South Carolina, 114 Doughty Street, Rm. 302 Charleston, SC 29403, United States. Tel.: +1 843 876 5067, fax: +1 843 876 5068. Email address: scholzd{at}musc.edu

Objectives Active mRNA distribution in the form of ribonucleoproteinparticles moving along microtubules has been shown in severalcell types, but not yet in cardiocytes. This study addressestwo hypotheses: 1) a similar mRNA distribution mechanism operatesin cardiocytes; 2) decoration of microtubules with microtubule-associatedproteins compromises this distribution.

Methods To visualize ribonucleoproteins in cultured neonatalrat cardiocytes, they were transfected with vectors encodingzipcode binding protein-1 and Staufen fused with GFP. The velocityof microtubular transport and elongation were calculated ontime-lapse confocal pictures.

Results: ZBP-1 and Staufen labeled particles co-localized witheach other and with microtubules and moved along microtubulesover a distance of 1–20 µm with a mean speedof 80 nm/s. The average speed decreased about 50% afterdecoration of microtubules by adenoviral microtubule-associatedprotein-4 (MAP-4). The elongation speed measured using the GFP-taggedend-binding protein-1 exceeded 200 nm/s and was not influencedby MAP-4.

Conclusions: We demonstrate for the first time ribonucleoproteinparticles in cardiocytes, their microtubular-related movement,and its inhibition (but not of the microtubular elongation),by the MAP-4 decoration of microtubules.

KEYWORDS mRNA; Microtubule; Cardiocyte; Translocation

Time for primary review 23 days

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