The secretion of tropoelastin by chick-embryo artery cells

Abstract

Chymotryptic fingerprint analyses of tropoelastin a and tropoelastin b demonstrated a very close relationship between these two polypeptides synthesized in a cell-free system under the direction of chick-embryo polyribosomal mRNA. A similar study on tropoelastin polypeptides extracted in their hydroxylated and under-hydroxylated forms from artery cells incubated with [3H]valine in the absence and presence of alpha alpha'-bipyridine or 3,4-dehydroproline confirmed this close relationship and suggested that tropoelastins a and b are likely to be the products of a single gene. Pulse-chase experiments in which the synthesis and secretion of tropoelastin by artery cells were monitored demonstrated that, after a pulse with [3H]proline, the polypeptides rapidly appeared in the medium and the half-time of tropoelastin secretion was approx. 30 min. Further pulse-chase studies, in which [3H]tropoelastin contents of subcellular fractions were determined, showed that rough and smooth microsomal fractions contained maximal amounts of tropoelastin at different times. The quantity of tropoelastin in the smooth-microsomal fraction was always only a small proportion of that in the rough-microsomal fraction, suggesting rapid translocation of the polypeptides to the plasma membrane. Incubation of the cells with 0.1 mM-colchicine did not markedly alter the rate of secretion or the distribution of tropoelastin between the subcellular fractions, whereas when 1 microM-monensin was included in the incubations the polypeptides were retained in the rough microsomal fraction. The results are consistent with the proposal that tropoelastin may follow a pathway of secretion from rough endoplasmic reticulum to the plasma membrane via secretory vesicles.

Impaired Elastic-Fiber Assembly by Fibroblasts from Patients with Either Morquio B Disease or Infantile GM1-Gangliosidosis Is Linked to Deficiency in the 67-kD Spliced Variant of β-Galactosidase

“…Elsewhere, it has been shown that tropoelastin can also bind to other intracellular chaperones, such as BIP and the peptidyl-prolyl cis-trans isomerase (Davis et al 1998). Moreover, Saunders and Grant (1985) demonstrated that, in arterial SMC, 30%-40% of all synthesized tropoelastin is not transported through the endosomes and Golgi apparatus but can be rapidly secreted through vesicles budding off the rough endoplastic reticulum in close proximity to the plasma membrane. Thus, it is possible that, in certain cell types, this mechanism can compensate for the S-Gal deficiency and can assure production of normal-looking elastic fibers.…”

Biochemistry of tropoelastin

“…Translation of mRNA takes place on the surface of the rough endoplasmic reticulum (RER) and polypeptide chains are released into the lumen of the RER with the release of the signal peptide [96]. Tropoelastin is secreted to the plasma membrane via secretory vesicles [97,98] ; it is possible to accumulate tropoelastin in the RER and Golgi apparatus experimentally using inhibitors of protein trafficking [99]. Inhibition of secretion of tropoelastin results in intracellular degradation of the accumulated tropoelastin [99,100].…”

“…Cysteine proteases have been found to be responsible for the degradation seen when tropoelastin accumulates to a high level in the RER, a process which has been speculated to be a clearance mechanism for aberrant tropoelastin probably through proteasome participation [99]. Newly synthesised tropoelastin has been estimated to take from as little as 20Ϫ30 min to 1 h to be secreted into the extracellular space of chick embryo smooth muscle cells [98,101,102].…”

A definition of the intima of human arteries and of its atherosclerosis-prone regions. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association.

“…196 - 200 Both smooth muscle cells 121 - 201 -202 and endothelial cells 203 -204 have been reported to synthesize elastin.…”