Semaphorin 3A displays a punctate distribution on the surface of neuronal cells and interacts with proteoglycans in the extracellular matrix

TY - JOUR

T1 - Semaphorin 3A displays a punctate distribution on the surface of neuronal cells and interacts with proteoglycans in the extracellular matrix

AU - de Wit, Joris

AU - De Winter, Fred

AU - Klooster, Jan

AU - Verhaagen, J.

PY - 2005/5

Y1 - 2005/5

N2 - Secreted semaphorins are essential for neural development and continue to be expressed in subpopulations of adult neurons, where they subserve as yet unknown functions. We employed functional myc- and GFP-tagged Sema3A proteins to obtain insight in the localization of Sema3A in neuronal cells. Sema3A localized to both axons and dendrites of cortical neurons. GFP-Sema3A exhibited a characteristic punctate distribution on the surface of Neuro-2a cells, localized to migratory pathways of cultured cells, and co-localized with and induced clustering of its receptor component neuropilin-1. Treatment with excess glycosaminoglycans and chondroitinase ABC resulted in the removal of cell surface Sema3A. Heparin enhanced Sema3A's binding to neuropilin-1-expressing cells and potentiated its growth cone collapsing activity. Together, these results indicate that association with proteoglycans in the extracellular matrix of neuronal cells plays an important role in the localization of the chemorepulsive guidance cue Sema3A, and that this interaction may enhance its biological activity.

AB - Secreted semaphorins are essential for neural development and continue to be expressed in subpopulations of adult neurons, where they subserve as yet unknown functions. We employed functional myc- and GFP-tagged Sema3A proteins to obtain insight in the localization of Sema3A in neuronal cells. Sema3A localized to both axons and dendrites of cortical neurons. GFP-Sema3A exhibited a characteristic punctate distribution on the surface of Neuro-2a cells, localized to migratory pathways of cultured cells, and co-localized with and induced clustering of its receptor component neuropilin-1. Treatment with excess glycosaminoglycans and chondroitinase ABC resulted in the removal of cell surface Sema3A. Heparin enhanced Sema3A's binding to neuropilin-1-expressing cells and potentiated its growth cone collapsing activity. Together, these results indicate that association with proteoglycans in the extracellular matrix of neuronal cells plays an important role in the localization of the chemorepulsive guidance cue Sema3A, and that this interaction may enhance its biological activity.

KW - Animals

KW - Anticoagulants

KW - Cerebral Cortex

KW - Epitopes

KW - Extracellular Matrix Proteins

KW - Green Fluorescent Proteins

KW - Growth Cones

KW - Heparin

KW - Membrane Proteins

KW - Mice

KW - Neuroblastoma

KW - Neurons

KW - Neuropilin-1

KW - Protein Binding

KW - Proteoglycans

KW - Proto-Oncogene Proteins c-myc

KW - Rats

KW - Rats, Wistar

KW - Semaphorin-3A

KW - Tumor Cells, Cultured

KW - Journal Article

U2 - 10.1016/j.mcn.2004.12.009

DO - 10.1016/j.mcn.2004.12.009

M3 - Article

C2 - 15866045

SN - 1044-7431

VL - 29

SP - 40

EP - 55

JO - Molecular and Cellular Neurosciences

JF - Molecular and Cellular Neurosciences

IS - 1

ER -