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Genetic Engineering of Dictyostelium discoideum Cells Based on Selection and Growth on Bacteria
Published on: January 25, 2019
Mfsd8 Modulates Growth and the Early Stages of Multicellular Development in Dictyostelium discoideum
Shyong Quan Yap1, William D Kim1, Robert J Huber1,2
1Environmental and Life Sciences Graduate Program, Trent University, Peterborough, ON, Canada.
Abstract:
MFSD8 is a transmembrane protein that has been reported to transport chloride ions across the lysosomal membrane. Mutations in MFSD8 are associated with a subtype of Batten disease called CLN7 disease. Batten disease encompasses a family of 13 inherited neurodegenerative lysosomal storage diseases collectively referred to as the neuronal ceroid lipofuscinoses (NCLs). Previous work identified an ortholog of human MFSD8 in the social amoeba D. discoideum (gene: mfsd8, protein: Mfsd8), reported its localization to endocytic compartments, and demonstrated its involvement in protein secretion. In this study, we further characterized the effects of mfsd8 loss during D. discoideum growth and early stages of multicellular development. During growth, mfsd8 - cells displayed increased rates of proliferation, pinocytosis, and expansion on bacterial lawns. Loss of mfsd8 also increased cell size, inhibited cytokinesis, affected the intracellular and extracellular levels of the quorum-sensing protein autocrine proliferation repressor A, and altered lysosomal enzyme activity. During the early stages of development, loss of mfsd8 delayed aggregation, which we determined was at least partly due to impaired cell-substrate adhesion, defects in protein secretion, and alterations in lysosomal enzyme activity. Overall, these results show that Mfsd8 plays an important role in modulating a variety of processes during the growth and early development of D. discoideum.
Insights
Loss of the MFSD8 protein in Dictyostelium discoideum affects cell growth and development. Mfsd8 deficiency impacts cell proliferation, secretion, and lysosomal function, crucial for multicellular organism development.
Area of Science:
- Cell Biology
- Developmental Biology
- Biochemistry
Background:
- MFSD8 is a lysosomal transmembrane protein linked to CLN7 Batten disease.
- An ortholog of MFSD8 exists in Dictyostelium discoideum, localized to endocytic compartments and involved in protein secretion.
- Previous studies established the role of Mfsd8 in D. discoideum protein secretion.
Purpose of the Study:
- To investigate the function of Mfsd8 during the growth and early multicellular development of D. discoideum.
- To characterize the cellular and developmental consequences of mfsd8 loss in D. discoideum.
Main Methods:
- Comparative analysis of wild-type and mfsd8-deficient D. discoideum strains.
- Assessment of cellular processes including proliferation, pinocytosis, cytokinesis, and cell-substrate adhesion.
- Quantification of protein secretion and lysosomal enzyme activity.
- Analysis of quorum-sensing signaling pathways.
Main Results:
- mfsd8-deficient cells exhibited increased proliferation, pinocytosis, and expansion.
- Loss of mfsd8 led to larger cell size, impaired cytokinesis, and altered autocrine proliferation repressor A levels.
- Developmental studies revealed delayed aggregation in mfsd8-deficient cells, attributed to impaired cell-substrate adhesion and protein secretion defects.
- Lysosomal enzyme activity was altered in mfsd8-deficient cells during both growth and development.
Conclusions:
- Mfsd8 plays a significant role in regulating cellular processes during D. discoideum growth.
- Mfsd8 is critical for timely multicellular development in D. discoideum, influencing aggregation, adhesion, and secretion.
- These findings highlight Mfsd8's conserved importance in cellular and developmental functions across species.
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