An actin filament population defined by the tropomyosin Tpm3.1 regulates glucose uptake

Area of Science:

• Cell Biology
• Molecular Physiology
• Biochemistry

Background:

• The precise role of actin in GLUT4 glucose transporter vesicle trafficking to the plasma membrane (PM) remains unclear.
• Actin dynamics are critical for intracellular transport and membrane fusion events.

Purpose of the Study:

• To investigate the role of specific actin filaments, defined by tropomyosin Tpm3.1, in GLUT4 trafficking and glucose uptake.
• To elucidate the molecular mechanisms by which Tpm3.1 influences glucose homeostasis.

Main Methods:

• Analysis of Tpm3.1-overexpressing and Tpm3.1-null mouse models.
• Studies in 3T3-L1 adipocytes to assess the impact of Tpm3.1 inhibition on GLUT4 translocation.
• Biochemical assays to determine protein interactions (Tpm3.1, MyoIIA, Myo1c, sec8) and actin binding.

Main Results:

• Novel actin filaments regulated by Tpm3.1 were identified at glucose uptake sites in white adipose tissue (WAT) and skeletal muscle.
• Tpm3.1 overexpression increased insulin-stimulated glucose uptake, while Tpm3.1 deficiency increased sensitivity to high-fat diet effects.
• Inhibition of Tpm3.1 in adipocytes blocked insulin-stimulated GLUT4 translocation and glucose uptake.
• Tpm3.1 levels correlated with filamentous actin, sec8, and Myo1c levels in WAT and modulated MyoIIA and Myo1c interactions in adipocytes.

Conclusions:

• Tpm3.1 plays a critical role in regulating actin filament populations involved in GLUT4 vesicle trafficking.
• Tpm3.1 influences the engagement of MyoIIA for contractile force and limits Myo1c interaction with actin.
• The balance of Tpm3.1-dependent actin filaments is a key determinant of GLUT4 vesicle transport and fusion efficiency with the plasma membrane.