Calmodulin and In Vitro Regenerating Frog Sciatic Nerves: Release and Extracellular Effects

Abstract

Although calmodulin (CaM) is commonly considered to be an intracellular protein, it has been suggested lately that it is released and exerts functions extracellularly. In the present investigation this was studied in in vitro regenerating adult frog (Rana temporaria) sciatic nerves. Using a multi-compartment incubation chamber, the non-neuronal cells in the outgrowth region of such nerves were radiolabelled with amino acid precursors. Based on immunological criteria, these cells were shown to release CaM. When the nerves were treated with CaM, both the outgrowth of sensory axons and the injury-induced proliferation of non-neuronal cells were partially inhibited. The inhibitory effects occurred even when the incubation medium contained as little as 30 pM CaM. Furthermore, treatment with anti-CaM antibodies resulted in reduced outgrowth, which suggested that during normal conditions extracellular CaM is kept at an optimal concentration. Finally, conditioned medium was found to contain several CaM-binding proteins. The present findings may reflect an earlier unknown function of extracellular CaM in controlling various growth mechanisms in integrated tissues.

CyrA, a matricellular protein that modulates cell motility in Dictyostelium discoideum

“…Consistent with CyrA cleavage products binding to CaM, full-length CyrA bound CaM both intra-and extracellularly (Suarez et al, 2011). Extracellular CaM has been shown in other systems, however CyrA is the first extracellular CaMBP identified in Dictyostelium (Remgard et al, 1995;Ikezaki et al, 1999;Ma et al, 1999;Suarez et al, 2011). Suarez et al (2011) reported a protective role for CaM on CyrA proteolysis.…”

Apoplastic Calmodulin Receptor-like Binding Proteins in Suspension-cultured Cells of Arabidopsis thaliana

“…2 Based on these data, we hold the idea that the conserved CaM isoform somehow has more chance to be secreted actively into extracellular space by living cells through an unidentified pathway. To date, positive secretion of extracellular CaM was only observed in animal cells (30).…”

The Presence of a Heterotrimeric G Protein and Its Role in Signal Transduction of Extracellular Calmodulin in Pollen Germination and Tube Growth

“…In addition, we have reported that extracellular CaM has some biological significance in plant cells (Sun et al, 1994(Sun et al, , 1995bMa and Sun, 1997). Extracellular CaM was also able to stimulate cell proliferation (MacNeil et al, 1984Crocker et al, 1988), control the outgrowth of sensory axons (Remgard et al, 1995), and inhibit the release of tumor necrosis factors from monocytes and elastase from neutrophils (Houston et al, 1997) in animal systems.…”

“…CaM is also present extracellularly in human body fluids, including blood, saliva, urine, and milk (MacNeil et al, 1984Crocker et al, 1988;Remgard et al, 1995;Houston et al, 1997). Moreover, it has been observed that extracellular CaM is the result of positive secretion in both plant and animal systems (Sun et al, 1994(Sun et al, , 1995bRemgard et al, 1995).…”