Connexins: substrates and regulators of autophagy

Connexins mediate intercellular communication by assembling into hexameric channel complexes that act as hemichannels and gap junction channels. Most connexins are characterized by a very rapid turn-over in a variety of cell systems. The regulation of connexin turn-over by phosphorylation and ubiquitination events has been well documented. Moreover, different pathways have been implicated in connexin degradation, including proteasomal and lysosomal-based pathways. Only recently, autophagy emerged as an important connexin-degradation pathway for different connexin isoforms. As such, conditions well known to induce autophagy have an immediate impact on the connexin-expression levels. This is not only limited to experimental conditions but also several pathophysiological conditions associated with autophagy (dys)function affect connexin levels and their presence at the cell surface as gap junctions. Finally, connexins are not only substrates of autophagy but also emerge as regulators of the autophagy process. In particular, several connexin isoforms appear to recruit pre-autophagosomal autophagy-related proteins, including Atg16 and PI3K-complex components, to the plasma membrane, thereby limiting their availability and capacity for regulating autophagy.     

Connexins: substrates and regulators of autophagy

Connexins mediate intercellular communication by assembling into hexameric channel complexes that act as hemichannels and gap junction channels. Most connexins are characterized by a very rapid turn-over in a variety of cell systems. The regulation of connexin turn-over by phosphorylation and ubiquitination events has been well documented. Moreover, different pathways have been implicated in connexin degradation, including proteasomal and lysosomal-based pathways. Only recently, autophagy emerged as an important connexin-degradation pathway for different connexin isoforms. As such, conditions well known to induce autophagy have an immediate impact on the connexin-expression levels. This is not only limited to experimental conditions but also several pathophysiological conditions associated with autophagy (dys)function affect connexin levels and their presence at the cell surface as gap junctions. Finally, connexins are not only substrates of autophagy but also emerge as regulators of the autophagy process. In particular, several connexin isoforms appear to recruit pre-autophagosomal autophagy-related proteins, including Atg16 and PI3K-complex components, to the plasma membrane, thereby limiting their availability and capacity for regulating autophagy.

     

Autonomic neuropathy in Fabry disease: a prospective study using the Autonomic Symptom Profile and cardiovascular autonomic function tests

Background  

Fabry patients have symptoms and signs compatible with autonomic dysfunction. These symptoms and signs are considered to be due to impairment of the peripheral nervous system, but findings indicative of autonomic neuropathy in other diseases, such as orthostatic intolerance and male sexual dysfunction, are infrequently reported in Fabry disease. The aim of our study was to investigate autonomic symptoms and cardiovascular autonomic function in a large cohort of male and female Fabry patients.     

Source of immunoreactive inhibin in the chicken ovary.

High concentrations of immunoreactive inhibin were detected in the plasma of the laying domestic hen using a heterologous RIA validated for use in the chicken. Cessation of egg production induced by restricting the intake of nutrients decreased circulating inhibin to approximately 20% of its original concentration within 8 days, indicating that the ovary is the major source of the measured material. Dissection of ovarian follicles revealed that inhibin is nearly exclusively produced in the granulosa cell layer. When expressed per milligram cell protein the concentration of inhibin decreased significantly in granulosa layers of follicles of succeeding order in the hierarchy (F4 to F1). The concentration of progesterone increased in the granulosa layers of the same follicles whereas oestradiol in the surrounding theca layers decreased. In vitro culture of granulosa cells derived from follicles at different stages of development confirmed the decrease in inhibin secretion as a function of follicular growth observed in vivo. The granulosa cell inhibin secretion is stimulated by LH as well as by FSH, the former being the most effective one. The physiological significance of these changes in inhibin concentration during follicular maturation requires further investigation. It may be concluded, however, that the chicken presents a useful model for the study of the endocrine as well as the paracrine function of ovarian inhibin.