Extracellular heat shock protein 70 has novel functional effects on sea urchin eggs and coelomocytes

Abstract

Numerous reports document that the 70 kDa heat shock proteins are not only intracellular proteins but are also present in blood and other extracellular compartments. How they affect cell function from the extracellular space remains unclear. Using two well-characterized cell types from the sea urchin,we show that extracellular mixtures of the constitutive and inducible forms of the 70 kDa heat shock proteins (Hsc70 and Hsp70, respectively) have dramatic effects on initiation of cell division in fertilized eggs and on the clotting reaction of hypotonically stressed coelomocytes. In suspensions of fertilized eggs to which Hsc70 or a 2:3 mixture of Hsc and Hsp70 was added, progression to the first mitotic division was accelerated. Evidence is provided that the extracellular Hsc70 passes into the egg cells in an unconventional manner,being distributed through the cytoplasm, and that it may alter the intracellular signaling cascade initiated by sperm penetration. In coelomocytes that were stimulated by hypotonic shock to mimic injury, the spreading reaction of the clotting response was significantly inhibited when either Hsp70 or Hsc70 was in the medium. These results suggest that the presence of Hsc and/or Hsp70 in the extracellular fluid may promote mitosis of dividing cells and suppress the reactivity of immune system cells.

Heat-shock protein A8 restores sperm membrane integrity by increasing plasma membrane fluidity

“…These results were partly unexpected because of the wealth of literature supporting HSPA1A's role in the protection of different cell types (Beckmann et al 1990, Shi & Thomas 1992, Browne et al 2007. Furthermore, none of the HSPA1A and HSPA8 combinations had any effect on viability, suggesting that HSPA1A negates the positive effect that is observed with HSPA8 alone.…”

Sea urchin immune cells as sentinels of environmental stress

“…Growing evidence suggests that this mechanism also occurs in the sea urchin immune cells. In fact, Browne et al (2007) showed that extra-cellular mixtures of the constitutive and inducible forms of the Hsp70 (Hsc70 and Hsp70, respectively) are involved in the clotting reaction of hypotonically stressed sea urchin immune cells, probably promoting mitosis of dividing cells and inhibiting cell spreading. A shotgun proteomics analysis of the coelomic fluid of the purple sea urchin, Strongylocentrotus purpuratus injected with LPS identified 27 proteins belonging to the stress response and detoxification classes (Dheilly et al, 2013), validating the key role of stress sensing in the regulation of the sea urchin immune cell activation.…”

Biochemical characterization of the interaction between HspA1A and phospholipids

“…This initial report was followed by many investigators showing that several members of the Hsp70 protein family, including HspA1A, as well as several bacterial Hsp70 (DnaK) proteins interact specifically with multiple glycolipids and phospholipids. These include phosphatidylserine (PS), bis-(monoacylglycero)-phosphate (BMP), globoyltriaosyl-ceramide (Gb3), sulfo-glycolipids, and anandamide (Arispe and De Maio 2000;Arispe et al 2002Arispe et al , 2004Armijo et al 2014;Broquet et al 2003;Browne et al 2007;Chen et al 2005;Gehrmann et al 2008;Harada et al 2007Harada et al , 2014Harada et al , 2015Kirkegaard et al 2010;Mahalka et al 2014;McCallister et al 2015;Oddi et al 2009;Petersen et al 2010;Whetstone and Lingwood 2003). These reports demonstrate that, although Hsp70s do not contain known lipid-binding domains, they interact with specific lipids and this interaction is evolutionarily conserved.…”