Fig. 1.

SMC elastogenesis cascade. (1) Transcription of tropoelastin and its chaperone organizational matricellular proteins. (2) Tropoelastin and chaperone proteins assemble outside of the cell, with two major classes of interactions. One is mediated by fibulin-4, which binds to tropoelastin and facilitates cross-linking by lysyl oxidase (LOX). The other is mediated by fibulin-5, which binds tropoelastin together with lysyl oxidase-like 1 (LOXL-1). (3) Tropoelastin coacervates, or globules of tropoelastin and chaperone proteins, are formed. (4) Tropoelastin coacervates are deposited along the fibrillin-1 microfibril complex, with initial interaction mediated by LTBP-4. Note that many important steps of microfibril assembly prior to elastin deposition, including the involvement of fibronectin, are excluded here for clarity. (5) Deposited tropoelastin coacervates integrate within the fibrillin-1/LTBP-1/LTBP-2/fibronectin microfibril complex. (6) Cross-linking, via LOX and LOXL-1, occurs between deposited tropoelastin coacervates within the microfibril complex, opening the coacervate structure and forming mature, mechanically-competent elastic fibers. Illustration credit: Rick Henkel at Light House Artwork (rick@lighthouseartwork.com).