ABSTRACT
Most organelles within the exocytic and endocytic pathways typically acidify their interiors, a phenomenon that is known to be crucial for their optimal functioning in eukaryotic cells. This review highlights recent advances in our understanding of how Golgi acidity is maintained and regulated, and how its misregulation contributes to organelle dysfunction and disease. Both its biosynthetic products (glycans) and protein-sorting events are highly sensitive to changes in Golgi luminal pH and are affected in certain human disease states such as cancers and cutis laxa. Other potential disease states that are caused by, or are associated with, Golgi pH misregulation will also be discussed.
Subject(s)
Disease/etiology , Eukaryotic Cells/metabolism , Golgi Apparatus/metabolism , Organelles/metabolism , Cutis Laxa/etiology , Cutis Laxa/physiopathology , Cystic Fibrosis/etiology , Cystic Fibrosis/physiopathology , Endocytosis/physiology , Eukaryotic Cells/physiology , Exocytosis/physiology , Glycosylation , Golgi Apparatus/physiology , Humans , Hydrogen-Ion Concentration , Neoplasms/etiology , Neoplasms/physiopathology , Organelles/physiology , Pemphigus, Benign Familial/etiology , Pemphigus, Benign Familial/physiopathologySubject(s)
Pemphigus, Benign Familial/pathology , Scabies/complications , Aged , Biopsy, Needle , Female , Humans , Immunohistochemistry , Pemphigus, Benign Familial/etiology , Pemphigus, Benign Familial/physiopathology , Prognosis , Recurrence , Risk Assessment , Scabies/diagnosis , Severity of Illness IndexABSTRACT
In skin, desmosomes constitute critical adhesion complexes between adjacent keratinocytes that help maintain an intact epidermis. However, individual keratinocytes need to migrate and differentiate and therefore desmosomes must have an inherent dynamic capacity to assemble and disassemble. This review highlights the role of the different structural junctional components involved in desmosome formation and turnover, as well as the possible signalling processes and pathways that may be implicated in desmosome homeostasis. Clues to the intricate nature of desmosome assembly and disassembly have been derived from human inherited and acquired blistering skin diseases as well as animal models and basic cell biology studies. The key implications for understanding desmosome dynamics from these findings are summarized in this review.
Subject(s)
Desmosomes/metabolism , Blister/etiology , Calcium/physiology , Cell Adhesion/physiology , Darier Disease/etiology , Desmosomes/chemistry , Humans , Intercellular Junctions , Keratinocytes/metabolism , Pemphigus/etiology , Pemphigus, Benign Familial/etiology , Protein Kinase C/physiology , Structure-Activity RelationshipABSTRACT
A doença de Hailey-Hailey, ou pênfigo familiar benigno crônico (PFBC), foi descrita em 1939 pelos irmäos Heiley. É uma rara afecçäo hereditária que se caracteriza por lesões vesicobolhosas frágeis, sobre base eritematosa, deixando áreas erosivas e vegetantes em locais de atrito, como axilas, virilhas e pescoço. A histopatologia lembra o pênfigo vulgar, pois as lesões se formam por acantólise suprabasal epidérmica. Os autores relatam o caso de uma paciente cuja doença apresentava 30 anos de evoluçäo, com ocorrência de erupções semelhantes em outros familiares, mas de variada intensidade
Subject(s)
Humans , Acantholysis/physiopathology , Chromosome Aberrations , Pemphigus, Benign Familial/etiology , Pemphigus, Benign Familial/physiopathology , Skin Diseases, GeneticABSTRACT
Benign familial chronic pemphigus, or Hailey-Hailey disease, is a rare hereditary condition characterized by development of blisters at sites of friction such as the neck, axillae and groin. Contact sensitivity to topical medications is reported to be common and routine patch testing has been strongly advocated. We report a case of Hailey-Hailey disease in a 43-year-old veterinary surgeon who presented with an acute exacerbation of his disease caused by herpes simplex virus type 1 (HSV). Patch testing was carried out to exclude a coexistent contact dermatitis and was complicated by severe local blistering. We are reporting this case to remind clinicians that HSV is a recognized cause of exacerbations of this disease and to warn that patch testing is not without hazard.
