title: Ion channel activity of brain abundant protein BASP1 in planar lipid bilayers.
abstract: BASP1 (also known as CAP-23 and NAP-22) is a brain abundant myristoylated protein localized at the inner surface of the presynaptic plasma membrane. Emerging evidence suggests that BASP1 is critically involved in various cellular processes, in particular, in the accumulation of phosphatidylinositol-4,5-diphosphate (PIP(2)) in lipid raft microdomains. We have recently shown that BASP1 forms heterogeneously-sized oligomers and higher aggregates with an outward similarity to oligomers and protofibrils of amyloid proteins. However, BASP1 is not known to be related to any amyloid disease. In the present study, we show that BASP1 induces single channel currents across negatively-charged planar lipid bilayers (containing phosphatidylserine or PIP(2)) bathed in 0.1-0.2 M KCl (pH 7.5). By their characteristics, BASP1 channels are similar to amyloid protein channels. BASP1 channels exhibit multiple conductance levels, in the range 10-3000 pS, with the most frequently observed conductance state of approximately 50 pS. The channels demonstrate a linear current-voltage relationship and voltage-independent kinetics of opening and closing. Their K(+) to Cl(-) permeability ratio is approximately 14, indicating that BASP1 channels are cation-selective. The ion channel activity of BASP1 is in accordance with the pore-like structure of BASP1 oligomers observed by electron microscopy on a lipid monolayer. Neuronal protein GAP-43, which is functionally related to BASP1 and also forms oligomers, elicited no ion channel currents under the conditions used in the present study. Elucidation of the physiological or pathological roles of ion channel activity of membrane-bound BASP1 oligomers will help to define the precise mechanism of amyloid protein toxicity.
authors.affiliation: Laboratory of Ionic Channels of Cell Membranes, Institute of Cytology of RAS, St Petersburg, Russia.
authors.forename: Olga S
authors.initials: OS
authors.lastname: Ostroumova
authors.forename: Ludmila V
authors.initials: LV
authors.lastname: Schagina
authors.forename: Mark I
authors.initials: MI
authors.lastname: Mosevitsky
authors.forename: Vladislav V
authors.initials: VV
authors.lastname: Zakharov
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002417:Cattle; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D019922:GAP-43 Protein; D007473:Ion Channels; D008051:Lipid Bilayers; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins