Butyrophilin controls milk fat globule secretion.
The molecular mechanism underlying milk fat globule secretion in mammary epithelial cells ostensibly involves the formation of complexes between plasma membrane butyrophilin and cytosolic xanthine oxidoreductase. These complexes bind adipophilin in the phospholipid monolayer of milk secretory granules, the precursors of milk fat globules, enveloping the nascent fat globules in a layer of plasma membrane and pinching them off the cell. However, using freeze-fracture immunocytochemistry, we find these proteins in locations other than those previously inferred. Significantly, butyrophilin in the residual plasma membrane of the fat globule envelope is concentrated in a network of ridges that are tightly apposed to the monolayer derived from the secretory granule, and the ridges coincide with butyrophilin labeling in the globule monolayer. Therefore, we propose that milk fat globule secretion is controlled by interactions between plasma membrane butyrophilin and butyrophilin in the secretory granule phospholipid monolayer rather than binding of butyrophilin-xanthine oxidoreductase complexes to secretory granule adipophilin.
Robenek
Horst
H
*Leibniz-Institute for Arteriosclerosis Research, University of Münster, 48149 Münster, Germany; robenek@uni-muenster.de.
Hofnagel
Oliver
O
*Leibniz-Institute for Arteriosclerosis Research, University of Münster, 48149 Münster, Germany.
Buers
Insa
I
*Leibniz-Institute for Arteriosclerosis Research, University of Münster, 48149 Münster, Germany.
Lorkowski
Stefan
S
*Leibniz-Institute for Arteriosclerosis Research, University of Münster, 48149 Münster, Germany.
Schnoor
Michael
M
*Leibniz-Institute for Arteriosclerosis Research, University of Münster, 48149 Münster, Germany.
Robenek
Mirko J
MJ
*Leibniz-Institute for Arteriosclerosis Research, University of Münster, 48149 Münster, Germany.
Heid
Hans
H
Division of Cell Biology, German Cancer Research Center, 69120 Heidelberg, Germany; and.
Troyer
David
D
*Leibniz-Institute for Arteriosclerosis Research, University of Münster, 48149 Münster, Germany.
Severs
Nicholas J
NJ
National Heart and Lung Institute, Imperial College, London SW3 6LY, United Kingdom.
D000906:Antibodies / Q000276:immunology; D000071797:Butyrophilins; D020285:Cryoelectron Microscopy; D005614:Freeze Fracturing; D006017:Glycolipids / Q000276:immunology / Q000378:metabolism*; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D066292:Lipid Droplets; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D008856:Microscopy, Fluorescence
D000906:Antibodies; D000071797:Butyrophilins; D006017:Glycolipids; D006023:Glycoproteins; D008562:Membrane Glycoproteins; C110367:milk fat globule