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1.
J Invest Dermatol ; 142(4): 1020-1025, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35051379

RESUMO

In this perspective, we focus on the skin epidermis and take you on a journey that highlights the adhesive- and cell shape‒changing adventures of a keratinocyte while it travels through the different layers of the epidermis, which is essential to make, maintain, and repair this barrier.


Assuntos
Adesivos , Queratinócitos , Forma Celular , Células Epidérmicas , Epiderme
2.
Biol Rev Camb Philos Soc ; 95(3): 592-624, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31970855

RESUMO

The nervous system communicates with peripheral tissues through nerve fibres and the systemic release of hypothalamic and pituitary neurohormones. Communication between the nervous system and the largest human organ, skin, has traditionally received little attention. In particular, the neuro-regulation of sebaceous glands (SGs), a major skin appendage, is rarely considered. Yet, it is clear that the SG is under stringent pituitary control, and forms a fascinating, clinically relevant peripheral target organ in which to study the neuroendocrine and neural regulation of epithelia. Sebum, the major secretory product of the SG, is composed of a complex mixture of lipids resulting from the holocrine secretion of specialised epithelial cells (sebocytes). It is indicative of a role of the neuroendocrine system in SG function that excess circulating levels of growth hormone, thyroxine or prolactin result in increased sebum production (seborrhoea). Conversely, growth hormone deficiency, hypothyroidism, and adrenal insufficiency result in reduced sebum production and dry skin. Furthermore, the androgen sensitivity of SGs appears to be under neuroendocrine control, as hypophysectomy (removal of the pituitary) renders SGs largely insensitive to stimulation by testosterone, which is crucial for maintaining SG homeostasis. However, several neurohormones, such as adrenocorticotropic hormone and α-melanocyte-stimulating hormone, can stimulate sebum production independently of either the testes or the adrenal glands, further underscoring the importance of neuroendocrine control in SG biology. Moreover, sebocytes synthesise several neurohormones and express their receptors, suggestive of the presence of neuro-autocrine mechanisms of sebocyte modulation. Aside from the neuroendocrine system, it is conceivable that secretion of neuropeptides and neurotransmitters from cutaneous nerve endings may also act on sebocytes or their progenitors, given that the skin is richly innervated. However, to date, the neural controls of SG development and function remain poorly investigated and incompletely understood. Botulinum toxin-mediated or facial paresis-associated reduction of human sebum secretion suggests that cutaneous nerve-derived substances modulate lipid and inflammatory cytokine synthesis by sebocytes, possibly implicating the nervous system in acne pathogenesis. Additionally, evidence suggests that cutaneous denervation in mice alters the expression of key regulators of SG homeostasis. In this review, we examine the current evidence regarding neuroendocrine and neurobiological regulation of human SG function in physiology and pathology. We further call attention to this line of research as an instructive model for probing and therapeutically manipulating the mechanistic links between the nervous system and mammalian skin.


Assuntos
Encéfalo/fisiologia , Glândulas Sebáceas/inervação , Glândulas Sebáceas/metabolismo , Fenômenos Fisiológicos da Pele , Pele/patologia , Animais , Dopamina/metabolismo , Hormônio do Crescimento/metabolismo , Humanos , Sistema Hipotálamo-Hipofisário/fisiologia , Sistemas Neurossecretores/fisiologia , Sistema Nervoso Periférico/fisiologia , Prolactina/metabolismo , Glândulas Sebáceas/anatomia & histologia , Glândulas Sebáceas/citologia , Sebo/química , Sebo/metabolismo , Somatomedinas/metabolismo , Células-Tronco , Glândula Tireoide/fisiologia
3.
J Biol Chem ; 290(8): 4801-4812, 2015 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-25568311

RESUMO

TET proteins oxidize 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine and thus provide a possible means for active DNA demethylation in mammals. Although their catalytic mechanism is well characterized and the catalytic dioxygenase domain is highly conserved, the function of the regulatory regions (the N terminus and the low-complexity insert between the two parts of the dioxygenase domains) is only poorly understood. Here, we demonstrate that TET proteins are subject to a variety of post-translational modifications that mostly occur at these regulatory regions. We mapped TET modification sites at amino acid resolution and show for the first time that TET1, TET2, and TET3 are highly phosphorylated. The O-linked GlcNAc transferase, which we identified as a strong interactor with all three TET proteins, catalyzes the addition of a GlcNAc group to serine and threonine residues of TET proteins and thereby decreases both the number of phosphorylation sites and site occupancy. Interestingly, the different TET proteins display unique post-translational modification patterns, and some modifications occur in distinct combinations. In summary, our results provide a novel potential mechanism for TET protein regulation based on a dynamic interplay of phosphorylation and O-GlcNAcylation at the N terminus and the low-complexity insert region. Our data suggest strong cross-talk between the modification sites that could allow rapid adaption of TET protein localization, activity, or targeting due to changing environmental conditions as well as in response to external stimuli.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Dioxigenases/metabolismo , N-Acetilglucosaminiltransferases/metabolismo , Processamento de Proteína Pós-Traducional/fisiologia , Proteínas Proto-Oncogênicas/metabolismo , Acetilglucosamina , Acilação/fisiologia , Proteínas de Ligação a DNA/genética , Dioxigenases/genética , Células HEK293 , Humanos , Oxigenases de Função Mista , N-Acetilglucosaminiltransferases/genética , Fosforilação/fisiologia , Estrutura Terciária de Proteína , Transporte Proteico/fisiologia , Proteínas Proto-Oncogênicas/genética
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