Sidekicks: synaptic adhesion molecules that promote lamina-specific connectivity in the retina.
A major determinant of specific connectivity in the central nervous system is that synapses made by distinct afferent populations are restricted to particular laminae in their target area. We identify Sidekick (Sdk)-1 and -2, homologous transmembrane immunoglobulin superfamily molecules that mediate homophilic adhesion in vitro and direct laminar targeting of neurites in vivo. sdk-1 and -2 are expressed by nonoverlapping subsets of retinal neurons; each sdk is expressed by presynaptic (amacrine and bipolar) and postsynaptic (ganglion) cells that project to common inner plexiform (synaptic) sublaminae. Sdk proteins are concentrated at synaptic sites, and Sdk-positive synapses are restricted to the 2 (of > or =10) sublaminae to which sdk-expressing cells project. Ectopic expression of Sdk in Sdk-negative cells redirects their processes to a Sdk-positive sublamina. These results implicate Sdks as determinants of lamina-specific synaptic connectivity.
Yamagata
Masahito
M
Department of Anatomy and Neurobiology, School of Medicine, Washington University, Saint Louis, MO 63110, USA.
Weiner
Joshua A
JA
Sanes
Joshua R
JR
D025042:Amacrine Cells / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion; D002645:Chickens; D029721:Drosophila Proteins; D005136:Eye Proteins / Q000737:chemistry / Q000502:physiology; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology; D008969:Molecular Sequence Data; D019006:Neural Cell Adhesion Molecules / Q000737:chemistry / Q000502:physiology*; D012160:Retina / Q000166:cytology / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000502:physiology; D013569:Synapses
D029721:Drosophila Proteins; D005136:Eye Proteins; D008565:Membrane Proteins; D019006:Neural Cell Adhesion Molecules; C108528:sdk protein, Drosophila