BAD-LAMP defines a subset of early endocytic organelles in subpopulations of cortical projection neurons.
The brain-associated LAMP-like molecule (BAD-LAMP) is a new member of the family of lysosome associated membrane proteins (LAMPs). In contrast to other LAMPs, which show a widespread expression, BAD-LAMP expression in mice is confined to the postnatal brain and therein to neuronal subpopulations in layers II/III and V of the neocortex. Onset of expression strictly parallels cortical synaptogenesis. In cortical neurons, the protein is found in defined clustered vesicles, which accumulate along neurites where it localizes with phosphorylated epitopes of neurofilament H. In primary neurons, BAD-LAMP is endocytosed, but is not found in classical lysosomal/endosomal compartments. Modification of BAD-LAMP by addition of GFP revealed a cryptic lysosomal retention motif, suggesting that the cytoplasmic tail of BAD-LAMP is actively interacting with, or modified by, molecules that promote its sorting away from lysosomes. Analysis of BAD-LAMP endocytosis in transfected HeLa cells provided evidence that the protein recycles to the plasma membrane through a dynamin/AP2-dependent mechanism. Thus, BAD-LAMP is an unconventional LAMP-like molecule and defines a new endocytic compartment in specific subtypes of cortical projection neurons. The striking correlation between the appearance of BAD-LAMP and cortical synatogenesis points towards a physiological role of this vesicular determinant for neuronal function.
David
Alexandre
A
Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Case 906, 13288 Marseille cedex 9, France. cremer@ibdm.univ-mrs.fr
Tiveron
Marie-Catherine
MC
Defays
Axel
A
Beclin
Christophe
C
Camosseto
Voahirana
V
Gatti
Evelina
E
Cremer
Harold
H
Pierre
Philippe
P
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D017124:Conserved Sequence; D003545:Cysteine / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry; D034281:Dynamins / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D051907:Lysosomal Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008247:Lysosomes / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014162:Transfection
D004220:Disulfides; D051907:Lysosomal Membrane Proteins; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins; D034281:Dynamins; D003545:Cysteine