RAB-10 Promotes EHBP-1 Bridging of Filamentous Actin and Tubular Recycling Endosomes.
EHBP-1 (Ehbp1) is a conserved regulator of endocytic recycling, acting as an effector of small GTPases including RAB-10 (Rab10). Here we present evidence that EHBP-1 associates with tubular endosomal phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] enriched membranes through an N-terminal C2-like (NT-C2) domain, and define residues within the NT-C2 domain that mediate membrane interaction. Furthermore, our results indicate that the EHBP-1 central calponin homology (CH) domain binds to actin microfilaments in a reaction that is stimulated by RAB-10(GTP). Loss of any aspect of this RAB-10/EHBP-1 system in the C. elegans intestinal epithelium leads to retention of basolateral recycling cargo in endosomes that have lost their normal tubular endosomal network (TEN) organization. We propose a mechanism whereby RAB-10 promotes the ability of endosome-bound EHBP-1 to also bind to the actin cytoskeleton, thereby promoting endosomal tubulation.
Department of Medical Genetics, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Peixiang
P
Wang
Department of Medical Genetics, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Hang
H
Liu
Department of Medical Genetics, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Yu
Y
Wang
Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey, United States of America.
Ou
O
Liu
Department of Medical Genetics, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Jing
J
Zhang
Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey, United States of America.
Adenrele
A
Gleason
Department of Medical Genetics, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Zhenrong
Z
Yang
Department of Medical Genetics, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Hui
H
Wang
Department of Medical Genetics, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.|Institute for Brain Research, Huazhong University of Science and Technology, Wuhan, Hubei, China.|Key Laboratory of Neurological Disease of National Education Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Anbing
A
Shi
Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey, United States of America.
Barth D
BD
Grant
D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D017173:Caenorhabditis elegans / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology; D011992:Endosomes / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D033921:Vesicular Transport Proteins / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
D000199:Actins; D029742:Caenorhabditis elegans Proteins; C555715:EHBP-1 protein, C elegans; D019269:Phosphatidylinositol 4,5-Diphosphate; D033921:Vesicular Transport Proteins; C510977:RAB-10 protein, C elegans; D020691:rab GTP-Binding Proteins