Diverging impact of cell fate determinants Scrib and Llgl1 on adhesion and migration of hematopoietic stem cells
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Diverging impact of cell fate determinants Scrib and Llgl1 on adhesion and migration of hematopoietic stem cells. / Dash, Banaja P; Schnöder, Tina M; Kathner, Carolin; Mohr, Juliane; Weinert, Sönke; Herzog, Carolin; Godavarthy, Parimala Sonika; Zanetti, Costanza; Perner, Florian; Braun-Dullaeus, Rüdiger; Hartleben, Björn; Huber, Tobias B; Walz, Gerd; Naumann, Michael; Ellis, Sarah; Vasioukhin, Valera; Kähne, Thilo; Krause, Daniela S; Heidel, Florian H.
In: J CANCER RES CLIN, Vol. 144, No. 10, 10.2018, p. 1933-1944.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Diverging impact of cell fate determinants Scrib and Llgl1 on adhesion and migration of hematopoietic stem cells
AU - Dash, Banaja P
AU - Schnöder, Tina M
AU - Kathner, Carolin
AU - Mohr, Juliane
AU - Weinert, Sönke
AU - Herzog, Carolin
AU - Godavarthy, Parimala Sonika
AU - Zanetti, Costanza
AU - Perner, Florian
AU - Braun-Dullaeus, Rüdiger
AU - Hartleben, Björn
AU - Huber, Tobias B
AU - Walz, Gerd
AU - Naumann, Michael
AU - Ellis, Sarah
AU - Vasioukhin, Valera
AU - Kähne, Thilo
AU - Krause, Daniela S
AU - Heidel, Florian H
PY - 2018/10
Y1 - 2018/10
N2 - PURPOSE: Cell fate determinants Scrib and Llgl1 influence self-renewal capacity of hematopoietic stem cells (HSCs). Scrib-deficient HSCs are functionally impaired and lack sufficient repopulation capacity during serial transplantation and stress. In contrast, loss of Llgl1 leads to increased HSC fitness, gain of self-renewal capacity and expansion of the stem cell pool. Here, we sought to assess for shared and unique molecular functions of Llgl1 and Scrib by analyzing their interactome in hematopoietic cells.METHODS: Interactome analysis was performed by affinity purification followed by mass spectrometry. Motility, migration and adhesion were assessed on primary murine HSCs, which were isolated by FACS sorting following conditional deletion of Scrib or Llgl1, respectively. Imaging of Scrib-deficient HSCs was performed by intravital 2-photon microscopy.RESULTS: Comparison of Scrib and Llgl1 interactome analyses revealed involvement in common and unique cellular functions. Migration and adhesion were among the cellular functions connected to Scrib but not to Llgl1. Functional validation of these findings confirmed alterations in cell adhesion and migration of Scrib-deficient HSCs in vitro and in vivo. In contrast, genetic inactivation of Llgl1 did not affect adhesion or migratory capacity of hematopoietic stem cells.CONCLUSION: Our data provide first evidence for an evolutionarily conserved role of the cell fate determinant Scrib in HSC adhesion and migration in vitro and in vivo, a unique function that is not shared with its putative complex partner Llgl1.
AB - PURPOSE: Cell fate determinants Scrib and Llgl1 influence self-renewal capacity of hematopoietic stem cells (HSCs). Scrib-deficient HSCs are functionally impaired and lack sufficient repopulation capacity during serial transplantation and stress. In contrast, loss of Llgl1 leads to increased HSC fitness, gain of self-renewal capacity and expansion of the stem cell pool. Here, we sought to assess for shared and unique molecular functions of Llgl1 and Scrib by analyzing their interactome in hematopoietic cells.METHODS: Interactome analysis was performed by affinity purification followed by mass spectrometry. Motility, migration and adhesion were assessed on primary murine HSCs, which were isolated by FACS sorting following conditional deletion of Scrib or Llgl1, respectively. Imaging of Scrib-deficient HSCs was performed by intravital 2-photon microscopy.RESULTS: Comparison of Scrib and Llgl1 interactome analyses revealed involvement in common and unique cellular functions. Migration and adhesion were among the cellular functions connected to Scrib but not to Llgl1. Functional validation of these findings confirmed alterations in cell adhesion and migration of Scrib-deficient HSCs in vitro and in vivo. In contrast, genetic inactivation of Llgl1 did not affect adhesion or migratory capacity of hematopoietic stem cells.CONCLUSION: Our data provide first evidence for an evolutionarily conserved role of the cell fate determinant Scrib in HSC adhesion and migration in vitro and in vivo, a unique function that is not shared with its putative complex partner Llgl1.
KW - Animals
KW - Apoptosis
KW - Cell Adhesion
KW - Cell Differentiation
KW - Cell Lineage
KW - Cell Movement
KW - Cell Proliferation
KW - Cells, Cultured
KW - Hematopoietic Stem Cells
KW - Homeodomain Proteins
KW - Intracellular Signaling Peptides and Proteins
KW - Mice
KW - Mice, Inbred C57BL
KW - Protein Interaction Domains and Motifs
KW - Proteome
KW - Tumor Suppressor Proteins
KW - Journal Article
U2 - 10.1007/s00432-018-2724-3
DO - 10.1007/s00432-018-2724-3
M3 - SCORING: Journal article
C2 - 30083817
VL - 144
SP - 1933
EP - 1944
JO - J CANCER RES CLIN
JF - J CANCER RES CLIN
SN - 0171-5216
IS - 10
ER -