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Published on: July 1, 2020
Absence of platelet phenotype in mice lacking the motor protein myosin Va
Matthew T Harper1, Marion T J van den Bosch, Ingeborg Hers
1School of Physiology and Pharmacology, University of Bristol, Bristol, United Kingdom.
Background:
The motor protein myosin Va plays an important role in the trafficking of intracellular vesicles. Mutation of the Myo5a gene causes Griscelli syndrome type 1 in humans and the dilute phenotype in mice, which are both characterised by pigment dilution and neurological defects as a result of impaired vesicle transport in melanocytes and neuroendocrine cells. The role of myosin Va in platelets is currently unknown. Rab27 has been shown to be associated with myosin Va cargo vesicles and is known to be important in platelet dense granule biogenesis and secretion, a crucial event in thrombus formation. Therefore, we hypothesised that myosin Va may regulate granule secretion or formation in platelets.
Methodology/Principal Findings:
Platelet function was studied in vitro using a novel Myo5a gene deletion mouse model. Myo5a(-/-) platelets were devoid of myosin Va, as determined by immunoblotting, and exhibited normal expression of surface markers. We assessed dense granule, α-granule and lysosomal secretion, integrin α(IIb)β(3) activation, Ca(2+) signalling, and spreading on fibrinogen in response to collagen-related peptide or the PAR4 agonist, AYPGKF in washed mouse platelets lacking myosin Va or wild-type platelets. Surprisingly, Myo5a(-/-) platelets showed no significant functional defects in these responses, or in the numbers of dense and α-granules expressed.
Conclusion:
Despite the importance of myosin Va in vesicle transport in other cells, our data demonstrate this motor protein has no non-redundant role in the secretion of dense and α-granules or other functional responses in platelets.
Insights
Myosin Va, crucial for vesicle transport in other cells, does not play a significant role in platelet granule secretion or function, according to studies on Myo5a gene deletion mice.
Area of Science:
- Cell Biology
- Hematology
- Molecular Motors
Background:
- Myosin Va is a motor protein vital for intracellular vesicle transport.
- Mutations in the Myo5a gene cause Griscelli syndrome type 1 and dilute coat color in mice, affecting pigment and neuroendocrine cells.
- The function of myosin Va in platelets remained unexplored, despite its association with Rab27 and platelet granule biogenesis.
Purpose of the Study:
- To investigate the role of myosin Va in platelet function, specifically in granule secretion and formation.
- To determine if myosin Va is essential for platelet responses crucial to thrombus formation.
Main Methods:
- Utilized a novel Myo5a gene deletion mouse model for in vitro platelet studies.
- Analyzed platelet secretion (dense, α-granules, lysosomes), integrin activation, Ca(2+) signaling, and fibrinogen spreading.
- Confirmed absence of myosin Va in Myo5a(-/-) platelets via immunoblotting.
Main Results:
- Myosin Va-deficient platelets (Myo5a(-/-)) exhibited normal expression of surface markers.
- No significant defects were observed in dense granule, α-granule, or lysosomal secretion in Myo5a(-/-) platelets.
- Platelets lacking myosin Va showed normal integrin α(IIb)β(3) activation, Ca(2+) signaling, and spreading responses.
- The number of dense and α-granules in Myo5a(-/-) platelets was comparable to wild-type.
Conclusions:
- Myosin Va is not essential for the secretion of dense and α-granules in platelets.
- The motor protein myosin Va has no non-redundant role in key platelet functional responses.
- Despite its importance in other cell types, myosin Va's function in platelets is compensated by other mechanisms.
