The neuronal porosome complex in health and disease.
Cup-shaped secretory portals at the cell plasma membrane called porosomes mediate the precision release of intravesicular material from cells. Membrane-bound secretory vesicles transiently dock and fuse at the base of porosomes facing the cytosol to expel pressurized intravesicular contents from the cell during secretion. The structure, isolation, composition, and functional reconstitution of the neuronal porosome complex have greatly progressed, providing a molecular understanding of its function in health and disease. Neuronal porosomes are 15 nm cup-shaped lipoprotein structures composed of nearly 40 proteins, compared to the 120 nm nuclear pore complex composed of >500 protein molecules. Membrane proteins compose the porosome complex, making it practically impossible to solve its atomic structure. However, atomic force microscopy and small-angle X-ray solution scattering studies have provided three-dimensional structural details of the native neuronal porosome at sub-nanometer resolution, providing insights into the molecular mechanism of its function. The participation of several porosome proteins previously implicated in neurotransmission and neurological disorders, further attest to the crosstalk between porosome proteins and their coordinated involvement in release of neurotransmitter at the synapse.
Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Akshata R
AR
Naik
Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Kenneth T
KT
Lewis
Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201, USA bjena@med.wayne.edu.
Bhanu P
BP
Jena
D000818:Animals; D021961:Cell Membrane Structures / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure*; D006801:Humans; D046911:Macromolecular Substances / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D018625:Microscopy, Atomic Force; D008954:Models, Biological; D009474:Neurons / Q000502:physiology*; D011487:Protein Conformation; D053838:Scattering, Small Angle; D009435:Synaptic Transmission
D046911:Macromolecular Substances; D008565:Membrane Proteins
Neuronal porosome complex; neuronal disease; neurotransmission