Neuromuscular development is a multistep process and involves interactions among various extracellular and transmembrane molecules that facilitate the precise targeting of motor axons to synaptogenic regions of the target muscle. Collagenous proteins with transmembrane domains have recently emerged as molecules that play essential roles in multiple aspects of neuromuscular formation. Membrane-associated collagens with interrupted triple helices (MACITs) are classified as an unconventional subtype of the collagen superfamily and have been implicated in cell adhesion in a variety of tissues, including the neuromuscular system. Collagen XXV, the latest member of the MACITs, plays an essential role in motor axon growth within the developing muscle. In humans, loss-of-function mutations of collagen XXV result in developmental ocular motor disorders. In contrast, collagen XIII contributes to the formation and maintenance of neuromuscular junctions (NMJs), and disruption of its function leads to the congenital myasthenic syndrome. Transmembrane collagens are conserved not only in mammals but also in organisms such as C. elegans, where a single MACIT, COL-99, has been documented to function in motor innervation. Furthermore, in C. elegans, a collagen-like transmembrane protein, UNC-122, is implicated in the structural and functional integrity of the NMJ. This review article summarizes recent advances in understanding the roles of transmembrane collagens and underlying molecular mechanisms in multiple aspects of neuromuscular development and disorders.

神经肌肉的发育是一个多步骤的过程，涉及各种细胞外和跨膜分子之间的相互作用，这有助于将运动轴突精确靶向到目标肌肉的突触形成区域。具有跨膜结构域的胶原蛋白近来已成为在神经肌肉形成的多个方面起着重要作用的分子。具有三重螺旋中断（MACITs）的膜相关胶原蛋白被归类为胶原蛋白超家族的非常规亚型，并且与多种组织（包括神经肌肉系统）的细胞粘附有关。XXV胶原蛋白是MACITs的最新成员，在发育中的肌肉中运动轴突生长中起着至关重要的作用。在人类中，胶原蛋白XXV的功能丧失突变导致发育性眼球运动障碍。相比之下，胶原蛋白XIII有助于神经肌肉接头（NMJs）的形成和维持，其功能破坏会导致先天性肌无力综合症。跨膜胶原不仅在哺乳动物中而且在诸如秀丽隐杆线虫，其中单个MACIT（COL-99）已被证明可用于运动神经支配。此外，在秀丽隐杆线虫胶原样跨膜蛋白UNC-122与NMJ的结构和功能完整性有关。这篇综述文章总结了在理解跨膜胶原蛋白的作用和潜在的分子机制在神经肌肉发育和疾病的多个方面的最新进展。