Novel pathways of protein secretion

Introduction Intercellular communications are fundamental for many of the biological processes that are involved in the survival of living organisms, and secretory proteins are among the most important messengers in this network of information. Proteins destined for this function are endowed with a hydrophobic signal peptide which targets them to the endoplasmic reticulum (ER) and are released in the extracellular environment by a ‘classical’ pathway of constitutive or regulated secretion. However, in the early 1990s it became evident that non-classical mechanisms must exist for the secretion of some proteins which, despite their extracellular localisation and function, lack a signal peptide. Indeed, the family of these leaderless secretory proteins continues to grow and comprises proteins that, although apparently unrelated, share both structural and functional features. This chapter will review current hypotheses on the mechanisms underlying non-classical secretion and discuss their implications in the regulation of the inflammatory and immune response. The relevance of non-classical secretion pathways to molecular chaperone biology is also discussed in Chapters 2 and 12. Leaderless secretory proteins Secretory mechanisms that are discrete to the classical pathways appear early in evolution. Gram negative bacteria are endowed with many (up to six) types of secretion mechanisms that are, at least in part, independent of the general secretory pathway, the prototype being the haemolysin secretion system [1]. In addition, two pathways of secretion that avoid the ER exist in yeast.