LCRMP-1 is required for spermatogenesis and stabilises spermatid F-actin organization via the PI3K-Akt pathway

Abstract Long-form collapsin response mediator protein-1 (LCRMP-1) belongs to the CRMP family which comprises brain-enriched proteins responsible for axon guidance. However, its role in spermatogenesis remains unclear. Here we find that LCRMP-1 is abundantly expressed in the testis. To characterize...

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Main Authors: Jung-Hsuan Chang, Chia-Hua Chou, Jui-Ching Wu, Keng-Mao Liao, Wei-Jia Luo, Wei-Lun Hsu, Xuan-Ren Chen, Sung-Liang Yu, Szu-Hua Pan, Pan-Chyr Yang, Kang-Yi Su
Format: Article
Language:English
Published: Nature Portfolio 2023-04-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-023-04778-2
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author Jung-Hsuan Chang
Chia-Hua Chou
Jui-Ching Wu
Keng-Mao Liao
Wei-Jia Luo
Wei-Lun Hsu
Xuan-Ren Chen
Sung-Liang Yu
Szu-Hua Pan
Pan-Chyr Yang
Kang-Yi Su
author_facet Jung-Hsuan Chang
Chia-Hua Chou
Jui-Ching Wu
Keng-Mao Liao
Wei-Jia Luo
Wei-Lun Hsu
Xuan-Ren Chen
Sung-Liang Yu
Szu-Hua Pan
Pan-Chyr Yang
Kang-Yi Su
author_sort Jung-Hsuan Chang
collection DOAJ
description Abstract Long-form collapsin response mediator protein-1 (LCRMP-1) belongs to the CRMP family which comprises brain-enriched proteins responsible for axon guidance. However, its role in spermatogenesis remains unclear. Here we find that LCRMP-1 is abundantly expressed in the testis. To characterize its physiological function, we generate LCRMP-1-deficient mice (Lcrmp-1 −/− ). These mice exhibit aberrant spermiation with apoptotic spermatids, oligospermia, and accumulation of immature testicular cells, contributing to reduced fertility. In the seminiferous epithelial cycle, LCRMP-1 expression pattern varies in a stage-dependent manner. LCRMP-1 is highly expressed in spermatids during spermatogenesis and especially localized to the spermiation machinery during spermiation. Mechanistically, LCRMP-1 deficiency causes disorganized F-actin due to unbalanced signaling of F-actin dynamics through upregulated PI3K-Akt-mTOR signaling. In conclusion, LCRMP-1 maintains spermatogenesis homeostasis by modulating cytoskeleton remodeling for spermatozoa release.
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spelling doaj.art-00a2c279cbcf45a98307696afbe0f2ab2023-04-16T11:22:28ZengNature PortfolioCommunications Biology2399-36422023-04-016111510.1038/s42003-023-04778-2LCRMP-1 is required for spermatogenesis and stabilises spermatid F-actin organization via the PI3K-Akt pathwayJung-Hsuan Chang0Chia-Hua Chou1Jui-Ching Wu2Keng-Mao Liao3Wei-Jia Luo4Wei-Lun Hsu5Xuan-Ren Chen6Sung-Liang Yu7Szu-Hua Pan8Pan-Chyr Yang9Kang-Yi Su10Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan UniversityDepartment of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan UniversityDepartment of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan UniversityGenome and Systems Biology Degree Program, National Taiwan University and Academia SinicaDepartment of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan UniversityDepartment of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan UniversityGraduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan UniversityDepartment of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan UniversityGenome and Systems Biology Degree Program, National Taiwan University and Academia SinicaDepartment of Internal Medicine, College of Medicine, National Taiwan UniversityDepartment of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan UniversityAbstract Long-form collapsin response mediator protein-1 (LCRMP-1) belongs to the CRMP family which comprises brain-enriched proteins responsible for axon guidance. However, its role in spermatogenesis remains unclear. Here we find that LCRMP-1 is abundantly expressed in the testis. To characterize its physiological function, we generate LCRMP-1-deficient mice (Lcrmp-1 −/− ). These mice exhibit aberrant spermiation with apoptotic spermatids, oligospermia, and accumulation of immature testicular cells, contributing to reduced fertility. In the seminiferous epithelial cycle, LCRMP-1 expression pattern varies in a stage-dependent manner. LCRMP-1 is highly expressed in spermatids during spermatogenesis and especially localized to the spermiation machinery during spermiation. Mechanistically, LCRMP-1 deficiency causes disorganized F-actin due to unbalanced signaling of F-actin dynamics through upregulated PI3K-Akt-mTOR signaling. In conclusion, LCRMP-1 maintains spermatogenesis homeostasis by modulating cytoskeleton remodeling for spermatozoa release.https://doi.org/10.1038/s42003-023-04778-2
spellingShingle Jung-Hsuan Chang
Chia-Hua Chou
Jui-Ching Wu
Keng-Mao Liao
Wei-Jia Luo
Wei-Lun Hsu
Xuan-Ren Chen
Sung-Liang Yu
Szu-Hua Pan
Pan-Chyr Yang
Kang-Yi Su
LCRMP-1 is required for spermatogenesis and stabilises spermatid F-actin organization via the PI3K-Akt pathway
Communications Biology
title LCRMP-1 is required for spermatogenesis and stabilises spermatid F-actin organization via the PI3K-Akt pathway
title_full LCRMP-1 is required for spermatogenesis and stabilises spermatid F-actin organization via the PI3K-Akt pathway
title_fullStr LCRMP-1 is required for spermatogenesis and stabilises spermatid F-actin organization via the PI3K-Akt pathway
title_full_unstemmed LCRMP-1 is required for spermatogenesis and stabilises spermatid F-actin organization via the PI3K-Akt pathway
title_short LCRMP-1 is required for spermatogenesis and stabilises spermatid F-actin organization via the PI3K-Akt pathway
title_sort lcrmp 1 is required for spermatogenesis and stabilises spermatid f actin organization via the pi3k akt pathway
url https://doi.org/10.1038/s42003-023-04778-2
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