Abstract
Growth-associated protein 43 (GAP43) is found in skeletal muscle, localized near the calcium release units. In interaction with calmodulin (CaM), it indirectly modulates the activity of dihydropyridine and ryanodine Ca2+ channels. GAP43–CaM interaction plays a key role in intracellular Ca2+ homeostasis and, consequently, in skeletal muscle activity. The control of intracellular Ca2+ signaling is also an important functional requisite in cardiac physiology. The aim of this study is to define the impact of GAP43 on cardiac tissue at macroscopic and cellular levels, using GAP43 knockout (GAP43−/−) newborn C57/BL6 mice. Hearts from newborn GAP43−/− mice were heavier than hearts from wild-type (WT) ones. In these GAP43−/− hearts, histological section analyses revealed a thicker ventricular wall and interventricular septum with a reduced ventricular chamber area. In addition, increased collagen deposits between fibers and increased expression levels of myosin were observed in hearts from GAP43−/− mice. Cardiac tropism and rhythm are controlled by multiple intrinsic and extrinsic factors, including cellular events such those linked to intracellular Ca2+ dynamics, in which GAP43 plays a role. Our data revealed that, in the absence of GAP43, there were cardiac morphological alterations and signs of hypertrophy, suggesting that GAP43 could play a role in the functional processes of the whole cardiac muscle. This paves the way for further studies investigating GAP43 involvement in signaling dynamics at the cellular level.
Highlights
Growth-associated protein 43 (GAP43) is a highly conserved protein expressed in vertebrate species (Caprara et al 2014)
Western blot analyses revealed that myosin heavy chain (MYH) and MYH7 were both significantly overexpressed in GAP43−/− hearts compared with WT ones (Fig. 4a and b)
Our experiments are the first to demonstrate that GAP43 is expressed in heart muscle and that its expression levels are related to the tissue development
Summary
Growth-associated protein 43 (GAP43) is a highly conserved protein expressed in vertebrate species (Caprara et al 2014). GAP43 has been defined as a “sponge” for CaM, being able to bind CaM, sequester it away from its downstream targets, and release it in response to changes in intracellular C a2+ or to signals by PKC (Benowitz and Routtenberg 1997). In the latter signaling process, an important functional role is played by serine-41, which, when
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