title: Semaphorin 7A Promotes Chemokine-Driven Dendritic Cell Migration.
abstract: Dendritic cell (DC) migration is essential for efficient host defense against pathogens and cancer, as well as for the efficacy of DC-based immunotherapies. However, the molecules that induce the migratory phenotype of DCs are poorly defined. Based on a large-scale proteome analysis of maturing DCs, we identified the GPI-anchored protein semaphorin 7A (Sema7A) as being highly expressed on activated primary myeloid and plasmacytoid DCs in human and mouse. We demonstrate that Sema7A deficiency results in impaired chemokine CCL21-driven DC migration in vivo. Impaired formation of actin-based protrusions, resulting in slower three-dimensional migration, was identified as the mechanism underlying the DC migration defect. Furthermore, we show, by atomic force microscopy, that Sema7A decreases adhesion strength to extracellular matrix while increasing the connectivity of adhesion receptors to the actin cytoskeleton. This study demonstrates that Sema7A controls the assembly of actin-based protrusions that drive DC migration in response to CCL21.
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands;
authors.forename: Anoek
authors.initials: A
authors.lastname: van Rijn
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands;
authors.forename: Leonie
authors.initials: L
authors.lastname: Paulis
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands;
authors.forename: Joost
authors.identifier: http://orcid.org/0000-0002-9093-010X
authors.initials: J
authors.lastname: te Riet
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands;
authors.forename: Angela
authors.initials: A
authors.lastname: Vasaturo
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands;
authors.forename: Inge
authors.initials: I
authors.lastname: Reinieren-Beeren
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands;
authors.forename: Alie
authors.initials: A
authors.lastname: van der Schaaf
authors.affiliation: Department of Pediatric Oncology, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands; and.
authors.forename: Arthur J
authors.identifier: http://orcid.org/0000-0001-8030-1572
authors.initials: AJ
authors.lastname: Kuipers
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands;
authors.forename: Luuk P
authors.identifier: http://orcid.org/0000-0003-2678-6024
authors.initials: LP
authors.lastname: Schulte
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus Institute, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands.
authors.forename: Bart C
authors.identifier: http://orcid.org/0000-0003-4799-333X
authors.initials: BC
authors.lastname: Jongbloets
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus Institute, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands.
authors.forename: R Jeroen
authors.identifier: http://orcid.org/0000-0003-1631-6440
authors.initials: RJ
authors.lastname: Pasterkamp
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands; carl.figdor@radboudumc.nl sbuschow@gmail.com.
authors.forename: Carl G
authors.initials: CG
authors.lastname: Figdor
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands;
authors.forename: Annemiek B
authors.initials: AB
authors.lastname: van Spriel
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands; carl.figdor@radboudumc.nl sbuschow@gmail.com.
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Buschow
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D054421:Chemokine CCL21 / Q000378:metabolism*; D003713:Dendritic Cells / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism*; D058851:GPI-Linked Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D018625:Microscopy, Atomic Force; D034622:RNA Interference; D034741:RNA, Small Interfering; D039961:Semaphorins / Q000235:genetics / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D054421:Chemokine CCL21; D058851:GPI-Linked Proteins; D034741:RNA, Small Interfering; C118753:SEMA7A protein, human; C485571:Sema7a protein, mouse; D039961:Semaphorins