MAGI-2 regulates the organization of podocyte actin cytoskeleton through its interaction with α-actinin-4 and synaptopodin - International Society of Nephrology Events

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E-Poster

https://storage.unitedwebnetwork.com/files/1099/5c3798a70233b93f87e0c77d19cb142f.pdf

Abstract Title *

MAGI-2 regulates the organization of podocyte actin cytoskeleton through its interaction with α-actinin-4 and synaptopodin

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Presenter First Name

Katsuhiko

Presenter Surname

Asanuma

Co-author 1

Mariko Ida marihori1226@gmail.com Chiba University Nephrology Chiba Japan -

Co-author 2

Hiroyuki Yamada hyamada@kuhp.kyoto-u.ac.jp Kyoto University Nephrology Kyoto Japan -

Co-author 3

Shin-ichi Makino smakino0403@gmail.com Chiba University Nephrology Chiba Japan -

Co-author 4

Issei Okunaga i_okunaga@chiba-u.jp Chiba University Nephrology Chiba Japan -

Co-author 5

Kaho Yamasaki kahoyamasaki@chiba-u.jp Chiba University Nephrology Chiba Japan -

Co-author 6

Yasuhiro Yoshimura yyoshimura@chiba-u.jp Chiba University Nephrology Chiba Japan -

Co-author 7

Atsuhiro Taguchi ataguchi@chiba-u.jp Chiba University Nephrology Chiba Japan -

Co-author 8

Katsuhiko Asanuma kasanuma@chiba-u.jp Chiba University Nephrology Chiba Japan *

Co-author 9

-

Co-author 10

-

Co-author 11

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Co-author 12

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Co-author 13

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Co-author 14

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Co-author 15

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Introduction

The highly organized structure of podocytes, including interdigitating foot processes and their bridging slit diaphragms (SDs), is essential for preventing plasma protein leakage into the urine. Previously, we and others have shown that podocyte injury induces dynamic rearrangement of the actin cytoskeleton. We further demonstrated that the scaffolding protein MAGI-2 is critical for SD maintenance and podocyte survival in mouse. However, the precise mechanisms regulating actin cytoskeleton dynamics in podocytes remain poorly understood. In this study, we aimed to elucidate the functional role of MAGI-2 in controlling actin dynamics in podocytes.

Methods

The highly organized structure of podocytes, including interdigitating foot processes and their bridging slit diaphragms (SDs), is essential for preventing plasma protein leakage into the urine. Previously, we and others have shown that podocyte injury induces dynamic rearrangement of the actin cytoskeleton. We further demonstrated that the scaffolding protein MAGI-2 is critical for SD maintenance and podocyte survival in mouse. However, the precise mechanisms regulating actin cytoskeleton dynamics in podocytes remain poorly understood. In this study, we aimed to elucidate the functional role of MAGI-2 in controlling actin dynamics in podocytes.

Results

Immunostaining and super-resolution microscopy analyses revealed redistribution of synaptopodin (Synpo) and α-actinin-4 upon MAGI-2 knockout. Consistently, electron microscopy confirmed displacement of actin bundles, suggesting a role for MAGI-2 in regulating the localization of these cytoskeletal proteins in vivo. Biochemical analyses demonstrated that MAGI-2 directly binds to Synpo and α-actinin-4 via its distinct domains, forming a ternary complex. Overexpression of Synpo, α-actinin-4, and MAGI-2 promoted the formation and redistribution of actin bundles to cell–cell junctions in COS7 cells and cultured podocytes.

Conclusion

MAGI-2 facilitates actin cytoskeletal remodeling and spatial organization through direct interaction with Synpo and α-actinin-4. Our findings demonstrate that MAGI-2 plays a pivotal role in maintaining the functional integrity of podocytes by orchestrating cellular structure, thereby representing a potential novel therapeutic target for alleviating proteinuria and preserving kidney function.

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