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Review
. 2023 Jun 15:14:1206906.
doi: 10.3389/fimmu.2023.1206906. eCollection 2023.

Platelet formation and activation are influenced by neuronal guidance proteins

Linyan Tang  1 , Chao Liu  1 , Peter Rosenberger  1
Affiliations
Review

Platelet formation and activation are influenced by neuronal guidance proteins

Linyan Tang et al. Front Immunol. .

Abstract

Platelets are anucleate blood cells derived from megakaryocytes. They link the fundamental functions of hemostasis, inflammation and host defense. They undergo intracellular calcium flux, negatively charged phospholipid translocation, granule release and shape change to adhere to collagen, fibrin and each other, forming aggregates, which are key to several of their functions. In all these dynamic processes, the cytoskeleton plays a crucial role. Neuronal guidance proteins (NGPs) form attractive and repulsive signals to drive neuronal axon navigation and thus refine neuronal circuits. By binding to their target receptors, NGPs rearrange the cytoskeleton to mediate neuron motility. In recent decades, evidence has indicated that NGPs perform important immunomodulatory functions and influence platelet function. In this review, we highlight the roles of NGPs in platelet formation and activation.

Keywords: immunomodulation; inflammation; neuronal guidance protein; platelet; thrombosis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Role of NGP and cytoskeleton in platelet formation. Megakaryocytes (MKs) are differentiated from hematopoietic stem cells (HSCs), and their maturation is marked by the polyploidized nucleus and the formation of an invaginated membrane system. Mature MKs extend cytoplasmic branches, named proplatelets, into sinusoidal microvessels in the bone marrow and shed platelets. In this process, microtubules are fundamental for proplatelet protrusion and elongation. Actin polymerization plays an important role in the dynamic bending and branching of proplatelets. Actomyosin provides mechanical force for proplatelet segmental contraction and intermediate narrowing, by which the size of platelets is limited. The NGP known as Sema7A has been shown to regulate platelet formation by inhibiting MKs differentiation. This is the only known NGP with this capability.
Figure 2
Figure 2
Platelet activation is regulated by neuronal guidance proteins (NGPs). In resting platelets, the spectrin-based skeleton supports the plasma membrane and the open canalicular system (OCS), and the marginal microtubule coils maintain the characteristic discoid shape of platelets. When platelets are stimulated and activated, dense tubules release Ca2+ to the cytoplasm, which increases the Ca2+ concentration and subsequently activates the cytoskeletal system. Peripheral microtubule coils expand and fold into the cell center, promoting platelet shape change. F-actin polymerization promotes granule release, protein trafficking and activation, and lamellipodia and filopodia extension. EphrinB1-EphA4 EphB1, Sema4D-PlexinB1 CD72 and Sema7A facilitate platelet activation, while PlexinB2 and Slit2-Robo play inhibitory roles in this process.
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Grants and funding

This work was supported by DFG CRC/TR 240 “Platelets—Molecular, cellular and systemic functions in health and disease” (Project # 374031971) TP B07 and by DFG-RO 3671/14-1 (to PR).

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