Identification of macrophage/microglia activation factor (MAF) associated with late endosomes/lysosomes in microglial cells.
Damage to the central nervous system triggers rapid activation and specific migration of glial cells towards the lesion site. There, glial cells contribute heavily to secondary neuronal changes that take place after lesion. In an attempt to identify the molecular cues of glial activation following brain trauma we performed differential display reverse transcription-polymerase chain reaction screenings from lesioned and control hippocampus. Here we report on the identification of the macrophage/microglia activation factor (MAF), a new membrane protein with seven putative transmembrane domains. Expression analysis revealed that MAF is predominantly expressed in microglial cells in the brain, and is upregulated following brain lesion. Overexpression of MAF in non-glial cells shows an intracellular codistribution with the lysosomal marker endosome/lysosome-associated membrane protein-1 (lamp-1). Furthermore, MAF-transfected cells show that MAF is primarily associated with late endosomes/lysosomes, and that this association can be disrupted by activation of protein kinase C-dependent pathways. In conclusion, these results imply that MAF is involved in the dynamics of lysosomal membranes associated with microglial activation following brain lesion.
Bräuer
Anja U
AU
Institute of Cell Biology and Neurobiology, Center for Anatomy, Charité University Medical School Berlin, Philippstr. 12, D-10115 Berlin, Germany.
Nitsch
Robert
R
Savaskan
Nicolai E
NE
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001483:Base Sequence; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D018387:Codon, Initiator; D018388:Codon, Terminator; D011992:Endosomes / Q000378:metabolism*; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology / Q000293:injuries; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes / Q000378:metabolism*; D016215:Macrophage-Activating Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000378:metabolism*; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D016716:PC12 Cells; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D015703:Antigens, CD; D018387:Codon, Initiator; D018388:Codon, Terminator; D051907:Lysosomal Membrane Proteins; D016215:Macrophage-Activating Factors; D012333:RNA, Messenger