The Phospholamban Journey 4 Decades After Setting Out for Ithaka
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“As you set out for Ithaka, hope your voyage is a long one, full of adventure, full of discovery….. Keep Ithaka always in your mind. Arriving there is what you are destined for. But do not hurry the journey at all. Better if it lasts for years……Ithaka gave you the marvelous journey. Without her you would not have set out.”
The quote above from the poem Ithaka by K. Kavafis is based on Homer’s Odyssey (8th century BC) and focuses on Odysseus’ journey to return to his kingdom in Ithaka (Greek: Ιθάκη, Ithaki) after the Troy war. Odysseus encounters numerous challenges, hardships, setbacks, but also beautiful new experiences, knowledge, and wisdom during this long voyage. Kavafis describes a journey that is both Odysseus’ and ours as we set out on a discovery voyage in our scientific careers. The poet urges us to live for the journey rather than the expected end point. It is the accumulated knowledge and wisdom through the years of scientific wandering and discovery that make our journey fun and enjoyable. Consistent with the poem’s theme, a journey to understand the functional role of phospholamban started over 40 years ago, on its identification in the heart. In this viewpoint, we present the lessons, challenges, shifting paradigms, controversies, and limitations of the phospholamban journey, which has been full of adventure and full of discovery!
In the early 1970s, investigators were trying to determine whether the relaxation-promoting effects of catecholamines in the heart may also involve the sarcoplasmic reticulum (SR) function. Indeed, addition of cAMP (cyclic adenosine monophosphate) or PKA (protein kinase A) to crude microsomal vesicles increased calcium (Ca)-transport activity. Surprisingly, P32 labeling indicated that SERCA (sarcoplasmic reticulum Ca2+ ATPase 1) was not phosphorylated but another small protein of ≈22 000 Da.1 The identity …