ABSTRACT
Laminins, one of the major functional components of basement membranes, are found underlying endothelium, and encasing pericytes and smooth muscle cells in the vessel wall. Depending on the type of blood vessel (capillary, venule, postcapillary venule, vein or artery) and their maturation state, both the endothelial and mural cell phenotype vary, with associated changes in laminin isoform expression. Laminins containing the α4 and α5 chains are the major isoforms found in the vessel wall, with the added contribution of laminin α2 in larger vessels. We here summarize current data on the precise localization of these laminin isoforms and their receptors in the different layers of the vessel wall, and their potential contribution to vascular homeostasis.
Subject(s)
Basement Membrane/metabolism , Endothelium, Vascular/metabolism , Laminin/metabolism , Animals , Basement Membrane/cytology , Cell Differentiation , Dystroglycans/metabolism , Endothelium, Vascular/cytology , Extracellular Matrix/genetics , Extracellular Matrix/metabolism , Fluorescent Antibody Technique , Humans , Laminin/genetics , Mechanotransduction, Cellular , Mice , Muscle Contraction , Muscle, Smooth, Vascular/blood supply , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/cytology , Myocytes, Smooth Muscle/metabolism , Phenotype , Protein Isoforms/metabolism , Receptors, Laminin/genetics , Receptors, Laminin/metabolismABSTRACT
A class of mitochondria-penetrating peptides (MPPs) was studied in an effort to optimize their applications in the delivery of bioactive cargo to this therapeutically important organelle. The sequence requirements for mitochondrial entry were monitored, and it was discovered that while an alternating cationic/hydrophobic residue motif is not required, the inclusion of a stretch of adjacent cationic amino acids can impede access to the organelle. In addition, a variety of N- and C-terminal cargo were tested to determine if there are limitations to the lipophilicity, charge, or polarity of compounds that can be transported to mitochondria by MPPs. The results reported demonstrate that these peptide sequences are versatile transporters that will have a range of biological applications.
Subject(s)
Biological Transport , Biotin/metabolism , Chromans/metabolism , Mitochondria/metabolism , Models, Biological , Peptides/metabolism , Biotin/chemical synthesis , Biotin/chemistry , Chromans/chemical synthesis , Chromans/chemistry , Hydrophobic and Hydrophilic Interactions , Lysine/chemistry , Mitochondria/chemistry , Molecular Structure , Peptides/chemical synthesis , Peptides/chemistryABSTRACT
Mitochondria are the energy factories of the cell and also serve as a checkpoint regulating programmed cell death. Not surprisingly, dysfunctional mitochondria are implicated in a variety of diseases ranging from metabolic disorders to cancer. Treatment of these diseases through the delivery of targeted drugs, however, is impeded by the difficulty of penetrating the membranes that define this organelle. The properties of this barrier serve as a major obstacle to drug delivery and a lack of effective transporters has hindered the advancement of mitochondrial medicine. Recently, however, synthetic transporters that show promise for the mito-specific delivery of bioactive cargos have begun to emerge. This review summarizes the most exciting of these developments and discusses their applications.
