FIGURE 2.

Potential extracellular roles of heat shock proteins in development. Although the exact mechanisms remain unclear, extracellular α-crystallins have been shown to promote axon guidance and neurite extension through inhibition of RhoA-ROCK signaling. Other extracellular Hsps, namely Hsp70 and Hsp90, have been suggested to interact with the Hsp70-Hsp90-organizing protein (HOP) and promote neuronal and glial migration through receptors such as toll-like receptor 4 (TLR4). In contrast, extracellular HspB1 has been shown to inhibit vascular endothelial growth factor (VEGF)-A signaling and angiogenesis by direct inhibition of VEGF-A. Abbreviations: RhoA, Ras homolog gene family, member A; ROCK, Rho-associated protein kinase; PI3K, phosphoinositide 3-kinase; MMP, matrix metalloproteinase; NFκB, nuclear factor κ light chain enhancer of activated B cells.