Myelin Basic Protein Induces Morphological Changes in the Endocrine Pancreas

Abstract

To evaluate effects of circulating myelin basic protein (MBP) on the endocrine pancreas, we injected bovine MBP to Djungarian hamsters and studied the morphological changes induced by MBP and its immunocytochemical distribution by electron microscopy. After a treatment time of 5-40 min, some islets appeared severely damaged, especially at their peripheries and near the intraislet capillaries, while others showed minor or no changes. MBP-induced extracellular changes included partial disintegration of the collagen filament network surrounding the islet and the blood vessels. These changes correlated with the association of MBP with the collagen filament bundles and related structures. Intracellularly, the effect of MBP included formation of vacuoles, dilatation of rough ER and Golgi membranes, swelling and aggregation of mitochondria, and disruption of the membranes of part of the insulin and glucagon granules, as well as damage to some plasma membranes. In the damaged B cells, 16-62% of the insulin granules exhibited an enlarged pale core, compared to 1-2% in the control B cells. MBP was shown to associate with mitochondria and with various intracellular membranes in all islet cells. In the B cells, MBP was localized to the membranes of insulin granules, and it also associated with the cores of the granules. In the A cells, the association of MBP to the glucagon granules was mainly with the outsides of the membranes. Interaction of MBP with the secretion granules is suggested to play a role in MBP-induced insulin and glucagon release, and some hormone might be released by leakage. Association of MBP with mitochondria, Golgi structures, and ER may lead to changes in various cellular functions. Key Words: Electron microscopyInsulin granule-Islet of Langerhans-Membrane fusionMitochondria-Myelin basic protein.Myelin basic protein (MBP) is one of the most abundant proteins in the central nervous system (CNS) and accounts for approximately one-third of the total myelin protein. In most mammals the major form is the 18.5-kDa MBP, one of several MBP variants (1). A proposed role for MBP is the maintenance of the multilamellar structure of the myelin sheath by joining the opposite cytoplasmic faces of the membrane.MBP is able to aggregate and fuse lipid vesicles of various compositions by ionic or hydrophobic interactions and to release their contents in vitro (2). MBP also associates with itself and with other proteins (2) including intracellular proteins such as calmodulin (3) and actin (4). MBP-induced morphological changes in vitro in chicken erythrocytes (5) and functional changes in hu-

Myelin management by the 18.5‐kDa and 21.5‐kDa classic myelin basic protein isoforms

“…). [Free, cytoplasmic MBP has been demonstrated to cause aberrant internal membrane fusion in pancreatic islet cells, for example (Kolehmainen and Sormunen )]. It has also been suggested that the strong association of the basic protein with PI(4,5)P 2 plays a further role in its peripheral membrane‐targeting (Nawaz et al .…”

Myelin basic protein—diverse conformational states of an intrinsically unstructured protein and its roles in myelin assembly and multiple sclerosis

“…More recently, new evidence is accumulating that implicates some isoforms of MBP (such as the early developmental ones), in signal transduction pathways in myelination during development, and possibly remyelination attempts during MS (Dyer, , 2002Tosic et al, 2002;Filipovic et al, 2002). There are other, non-CNS phenomena; for example, MBP can induce insulin and glucagon release from pancreatic islets (Kolehmainen et al, 1990;Kolehmainen, 1995a,b;Kolehmainen and Sormunen, 1998 transmission electron microscope/y TFE 2,2,2-trifluoroethanol (CF 3 -CH 2 -OH) TFE-d 2 deuterated 2,2,2-trifluoroethanol (CF 3 -CD 2 -OH) TOCSY total correlation spectroscopy TRIS tris(hydroxymethyl)aminomethane TROSY transverse relaxation optimised spectroscopy of any member of this family, and only a few structures of other myelin proteins (Kursula, 2001). We can rationalise this situation in light of the recent realisation that all MBP isoforms are IUPs (Hill et al, , 2003.…”

Identification of Myelin Basic Protein Proximity Interactome Using TurboID Labeling Proteomics

“…We have previously shown the association of MBP with proteins from the translational machinery [ 26 ], and now these data are additionally confirmed. The importance of the association of MBP with mitochondria has been shown previously [ 74 , 75 , 76 ]. SRP-dependent cotranslational protein targeting to the membrane occurs during translation and is dependent upon two key components, the signal-recognition particle (SRP) and the SRP receptor.…”